Guro Elisabeth Lind

PMID: 12483540 (Oncogene, 2002)

PMID: 17029216 (J Pathol, 2006)

PMID: 17201907 (Mol Cancer, 2007)

PMID: 18281782 (Epigenetics, 2007)

PMID: 21154162 (Curr Opin Mol Ther, 2010)

PMID: 21305644 (Genes Chromosomes Cancer, 2011)

PMID: 21406965 (Epigenetics, 2011)
 

• Kranjec, Christian; Eilertsen, Ina; Nunes, Luis; Moosavi, Hossein; Berg, Kaja Christine Graue & Eknæs, Mette [Show all 12 contributors for this article] (2026). Common gene mutations in 103 authenticated colorectal cancer cell lines. Oncogenesis. 15. doi: 10.1038/s41389-026-00599-0. Full text in Research Archive Show summary

  Colorectal cancer (CRC) cell lines represent the main molecular subtypes of tumors and are valuable models for preclinical investigations. However, cell lines can diverge over time and careful selection of models based on their molecular features is key. We have authenticated 103 commonly used CRC cell lines and present the mutation profiles of 20 CRC-relevant genes sequenced to an average depth of 575 times coverage. The cell lines reflected the distinct mutation patterns of hypermutation phenotypes associated with microsatellite instability and pathogenic POLE mutations. Hypermutated cell lines appeared to have a stronger mutational divergence and more frequent subclonal mutations, while mutations not associated with hypermutation were more frequently homozygous or hemizygous, classified as pathogenic, and subject to stronger selection pressure. Loss of heterozygosity at mutated loci was primarily observed in tumor suppressor genes. Genetic interactions based on co-occurring mutations identified cell lines representative of particularly aggressive subtypes of CRC, including concurrent BRAF p.V600 and truncating APC mutations, as well as APC/TP53/RAS triple mutations with double hits of APC. This study provides a resource to guide the selection of cell lines for functional studies of CRC, and detailed mutation data including classifications of pathogenicity, variant allele frequencies and illustrations of the mutation distribution along the length of encoded proteins are included.

• Pharo, Heidi; Brandt-Winge, Sara; Thorkildsen, Evy Marie; Vedeld, Hege Marie & Lind, Guro Elisabeth (2025). DNA Methylation Analyses of Tissue Samples and Cell-Free DNA by Droplet Digital PCR. In Pavlovic, Guillaume (Eds.), Digital PCR. Springer Nature. ISSN 9781071647677. p. 179–194. doi: 10.1007/978-1-0716-4767-7_12. Full text in Research Archive
• Pinto, Rita Isabel Morais; Sjurgard, Ingrid Vikan; Pharo, Heidi; Mala, Tom; Vedeld, Hege Marie & Lind, Guro Elisabeth (2025). Molecular stratification of esophageal adenocarcinoma: implications for prognosis and treatment strategy. Oncogene. ISSN 0950-9232. 45, p. 353–367. doi: 10.1038/s41388-025-03650-3. Full text in Research Archive Show summary

  Genome-wide molecular profiling has emerged as a promising approach for advancing the clinical management of esophageal adenocarcinoma (EAC), with the potential to improve prognostic accuracy and enable more personalized treatment strategies. In this review, we summarize current evidence from genomic and epigenomic EAC stratification studies, highlighting the proposed molecular subtypes and evaluating their clinical relevance. We discuss how these subclassifications may inform disease outcomes, refine patient selection for specific therapies and uncover new treatment opportunities aligned with tumor molecular profiles. Additionally, we explore molecular subtypes associated with Barrett’s esophagus, a precursor lesion of EAC, and consider how these insights can help elucidate the mechanisms underlying EAC development. Such understanding may inform improved strategies for early tumor detection, risk stratification and prevention, ultimately aiming to reduce the burden of EAC. We also address the current challenges limiting the clinical application of these molecular classifiers, including restricted sample availability, insufficient validation and the difficulty of translating genome-wide findings into practical and clinical useful biomarkers. Integrating molecular subtyping into clinical workflows is a key step toward precision medicine in EAC, with the goal of enhancing treatment response rates and patient outcomes. Future advances will require collaborative efforts and robust clinical validation in large prospective studies to ensure that molecular stratification strategies can be effectively translated into improved management of EAC.

• Pharo, Heidi; Vedeld, Hege Marie; Sjurgard, Ingrid Vikan; Pinto, Rita Isabel Morais & Lind, Guro Elisabeth (2025). From concept to clinic: a roadmap for DNA methylation biomarkers in liquid biopsies. Oncogene. ISSN 0950-9232. 44, p. 4814–4831. doi: 10.1038/s41388-025-03624-5. Full text in Research Archive Show summary

  Global cancer incidence continues to rise, emphasizing the urgent need for improved diagnostics and management strategies. DNA methylation biomarkers in liquid biopsies offer a promising, minimally invasive solution. Despite their potential, only a few tests have successfully transitioned from research to clinical practice. This review addresses key aspects influencing successful biomarker development and clinical implementation—including liquid biopsy source selection, biomarker discovery workflow and targeted validation in clinical sample series—and provide strategies to improve accuracy, reproducibility and clinical utility. Altogether, these considerations could aid in bridging the translational gap from research to clinical application, and to increase the number of clinically implemented liquid biopsy tests.

• Kresse, Stine Henrichson; Thorkildsen, Evy Marie; Brandt-Winge, Sara; Pharo, Heidi; Vedeld, Hege Marie & Lind, Guro Elisabeth (2025). Comparison of enzymatic and bisulfite conversion of circulating cell-free tumor DNA for DNA methylation analyses. Clinical Epigenetics. 1(17). doi: 10.1186/s13148-025-01901-4. Full text in Research Archive Show summary

  Background Detection of DNA methylation biomarkers in circulating cell-free DNA (cfDNA) has great clinical potential for cancer management, but there is a high need for method optimization and standardization. Bisulfite conversion of DNA is the gold-standard pre-treatment method for DNA methylation analyses, but causes also DNA fragmentation and loss. Enzymatic conversion of DNA represents a promising alternative due to the more gentle treatment minimizing damage to DNA. The aim of this study was to evaluate and compare enzymatic and bisulfite conversion to identify the best pre-treatment method for detecting DNA methylation biomarkers in cfDNA from plasma using droplet digital PCR (ddPCR). Results The performance of the NEBNext Enzymatic Methyl-seq Kit (both the full kit intended for sequencing and the sub-component NEBNext Enzymatic Methyl-seq Conversion Module) and the EpiTect Plus DNA Bisulfite Kit was evaluated and compared using normal cfDNA and tumor cfDNA samples from colorectal cancer patients. The cytosine conversion efficiency was 99–100% for both enzymatic and bisulfite conversion. Enzymatic conversion resulted in longer DNA fragments with higher peak fragment sizes compared to bisulfite conversion, but the DNA recovery was considerably lower after enzymatic conversion (34–47%) compared to bisulfite conversion (61–81%). For enzymatic conversion, the full kit gave slightly better DNA recovery than the conversion module. A comparison of five magnetic bead brands, as well as several different magnetic bead-to-sample ratios revealed no major improvements in DNA recovery for the enzymatic conversion. DNA methylation of the biomarker BCAT1 was detected at similar rates in parallel tumor cfDNA samples pre-treated with either enzymatic or bisulfite conversion. However, enzymatic conversion resulted in lower number of positive droplets for both target and control ddPCR assays, in line with the lower DNA recovery after conversion. Conclusions Based on a thorough evaluation of enzymatic and bisulfite conversion of cfDNA using ddPCR, bisulfite conversion emerges as the best pre-treatment method due to higher DNA recovery after conversion and higher number of positive droplets in the ddPCR reactions.

• Pinto, Rita Isabel Morais; Vedeld, Hege Marie; Lind, Guro Elisabeth & Jeanmougin, Marine Anne-Lise Francoise (2024). Unraveling epigenetic heterogeneity across gastrointestinal adenocarcinomas through a standardized analytical framework. Molecular Oncology. ISSN 1574-7891. doi: 10.1002/1878-0261.13772. Full text in Research Archive Show summary

  In this study, we propose an alternative approach for stratifying genome-scale DNA methylation profiles of gastrointestinal (GI) adenocarcinomas based on a robust analytical framework. A set of 978 GI adenocarcinomas and 120 adjacent normal tissues from public repositories was quality controlled and analyzed. Hierarchical consensus clustering of the tumors, based on differential epigenetic variability between malignant and normal samples, identified six distinct subtypes defined either by a pan-GI or a lower GI-specific phenotype. In addition to methylation levels, aberrant methylation frequencies and the degree of DNA methylation instability contributed to the characterization of each subtype. We found significant differences in the outcome of patients, with the poorest overall survival seen for those belonging to a pan-GI subtype with infrequent aberrant methylation. In conclusion, our standardized approach contributes to a refined characterization of the epigenetic heterogeneity in GI adenocarcinomas, offering insights into subtype-specific methylation with the potential to support prognostication.

• Vedeld, Hege Marie; Pharo, Heidi Dietrichson; Sørbø, Anne; Brandt-Winge, Sara; Five, May-Britt & Jeanmougin, Marine Anne-Lise Francoise [Show all 9 contributors for this article] (2024). Distinct longitudinal patterns of urine tumor DNA in patients undergoing surveillance for bladder cancer. Molecular Oncology. ISSN 1574-7891. 18, p. 2684–2695. doi: 10.1002/1878-0261.13639. Full text in Research Archive Show summary

  Cystoscopy is the gold standard for surveillance of non-muscle invasive bladder cancer (NMIBC), but the procedure is invasive and has suboptimal accuracy. The aim of this study was to investigate the potential of analyzing urine samples for the presence of urine tumor DNA (utDNA) to replace cystoscopy for surveillance of bladder cancer recurrence. In this longitudinal, prospective, and observational study, 47 patients were followed for recurrence for 2 years, involving analysis of utDNA using the BladMetrix DNA methylation biomarker test at each cystoscopy. In total, utDNA was detected in 21/23 recurrences (91% sensitivity), including 5/5 T1, T2, and carcinoma in situ (CIS) tumors (100%) and 10/12 Ta tumors (83%), with < 1% false-negative test results. Importantly, utDNA analysis showed the potential to reduce the number of cystoscopies by 55%, benefitting 79% of the patients. Eleven of 23 recurrences (48%) were detected earlier with utDNA than with cystoscopy, and distinct patterns of residual utDNA post-surgery indicated minimal residual disease (MRD) or field effect in 6% and 15% of the patients, respectively. In conclusion, utDNA analysis shows high sensitivity to detect tumor recurrence, potential to reduce the number of cystoscopies, and promise to guide patient-specific surveillance regimens.

• Kresse, Stine Henrichson; Brandt-Winge, Sara; Pharo, Heidi Dietrichson; Flatin, Bjørnar Tovson Bae; Jeanmougin, Marine Anne-Lise Francoise & Vedeld, Hege Marie [Show all 7 contributors for this article] (2023). Evaluation of commercial kits for isolation and bisulfite conversion of circulating cell-free tumor DNA from blood. Clinical Epigenetics. 15(1). doi: 10.1186/s13148-023-01563-0. Full text in Research Archive Show summary

  Background DNA methylation biomarkers in circulating cell-free DNA (cfDNA) have great clinical potential for cancer management. Most methods for DNA methylation analysis require bisulfite conversion, causing DNA degradation and loss. This is particularly challenging for cfDNA, which is naturally fragmented and normally present in low amounts. The aim of the present study was to identify an optimal combination of cfDNA isolation and bisulfite conversion kits for downstream analysis of DNA methylation biomarkers in plasma. Results Of the five tested bisulfite conversion kits (EpiJET Bisulfite Conversion Kit, EpiTect Plus DNA Bisulfite Kit (EpiTect), EZ DNA Methylation-Direct Kit, Imprint DNA Modification Kit (Imprint) and Premium Bisulfite Kit), the highest and lowest DNA yield and recovery were achieved using the EpiTect kit and the Imprint kit, respectively, with more than double the amount of DNA for the EpiTect kit. Of the three tested cfDNA isolation kits (Maxwell RSC ccfDNA Plasma Kit, QIAamp Circulating Nucleic Acid Kit (CNA) and QIAamp MinElute ccfDNA Mini Kit), the CNA kit yielded around twice as much cfDNA compared to the two others kits, although with more high molecular weight DNA present. When comparing various combinations of cfDNA isolation kits and bisulfite conversion kits, the CNA kit and the EpiTect kit were identified as the best-performing combination, resulting in the highest yield of bisulfite converted cfDNA from normal plasma, as measured by droplet digital PCR (ddPCR). As a proof of principle, this kit combination was used to process plasma samples from 13 colorectal cancer patients for subsequent ddPCR methylation analysis of BCAT1 and IKZF1. Methylation of BCAT1 and/or IKZF1 was identified in 6/10 (60%) stage IV patients and 1/3 (33%) stage III patients. Conclusions Based on a thorough evaluation of five bisulfite conversion kits and three cfDNA isolation kits, both individually and in combination, the CNA kit and the EpiTect kit were identified as the best-performing kit combination, with highest DNA yield and recovery across a range of DNA input amounts. The combination was successfully used for detection of clinically relevant DNA methylation biomarkers in plasma from cancer patients.

• Jeanmougin, Marine Anne-Lise Francoise; Brodal, Hans Petter; Pharo, Heidi Dietrichson; Vedeld, Hege Marie & Lind, Guro Elisabeth (2023). PoDCall: positive droplet calling and normalization of droplet digital PCR DNA methylation data. Bioinformatics. ISSN 1367-4803. 39(1). doi: 10.1093/bioinformatics/btac766. Full text in Research Archive Show summary

  Abstract Motivation Droplet digital PCR (ddPCR) holds great promises for investigating DNA methylation with high sensitivity. Yet, the lack of methods for analyzing ddPCR DNA methylation data has resulted in users processing the data manually at the expense of standardization. Results PoDCall is an R package performing automated calling of positive droplets, quantification and normalization of methylation levels in ddPCR experiments. A Shiny application provides users with an intuitive and interactive interface to access PoDCall functionalities. Availability and implementation The PoDCall R package is freely available on Bioconductor at https://bioconductor.org/packages/PoDCall/. The Shiny application can be executed from the R console using the wrapper function PoDCall::podcallShiny(). Supplementary information Supplementary data are available at Bioinformatics online.

• Namløs, Heidi Maria; Skårn, Magne Nordang; Ali, Deeqa Ahmed Mohamed; Grad, Iwona; Andresen, Kim & Kresse, Stine Henrichson [Show all 13 contributors for this article] (2022). miR-486-5p expression is regulated by DNA methylation in osteosarcoma. BMC Genomics. 23(1). doi: 10.1186/s12864-022-08346-6. Full text in Research Archive Show summary

  Background Osteosarcoma is the most common primary malignant tumour of bone occurring in children and young adolescents and is characterised by complex genetic and epigenetic changes. The miRNA miR-486-5p has been shown to be downregulated in osteosarcoma and in cancer in general. Results To investigate if the mir-486 locus is epigenetically regulated, we integrated DNA methylation and miR-486-5p expression data using cohorts of osteosarcoma cell lines and patient samples. A CpG island in the promoter of the ANK1 host gene of mir-486 was shown to be highly methylated in osteosarcoma cell lines as determined by methylation-specific PCR and direct bisulfite sequencing. High methylation levels were seen for osteosarcoma patient samples, xenografts and cell lines based on quantitative methylation-specific PCR. 5-Aza-2′-deoxycytidine treatment of osteosarcoma cell lines caused induction of miR-486-5p and ANK1, indicating common epigenetic regulation in osteosarcoma cell lines. When overexpressed, miR-486-5p affected cell morphology. Conclusions miR-486-5p represents a highly cancer relevant, epigenetically regulated miRNA in osteosarcoma, and this knowledge contributes to the understanding of osteosarcoma biology.

• Pharo, Heidi Dietrichson; Jeanmougin, Marine; Ager-Wick, Eirill; Vedeld, Hege Marie; Sørbø, Anne & Dahl, Christina [Show all 17 contributors for this article] (2022). BladMetrix: a novel urine DNA methylation test with high accuracy for detection of bladder cancer in hematuria patients. Clinical Epigenetics. 14(1). doi: 10.1186/s13148-022-01335-2. Full text in Research Archive Show summary

  Background Cystoscopy is the gold standard for bladder cancer detection, but is costly, invasive and has imperfect diagnostic accuracy. We aimed to identify novel and accurate DNA methylation biomarkers for non-invasive detection of bladder cancer in urine, with the potential to reduce the number of cystoscopies among hematuria patients. Results Biomarker candidates (n = 32) were identified from methylome sequencing of urological cancer cell lines (n = 16) and subjected to targeted methylation analysis in tissue samples (n = 60). The most promising biomarkers (n = 8) were combined into a panel named BladMetrix. The performance of BladMetrix in urine was assessed in a discovery series (n = 112), consisting of bladder cancer patients, patients with other urological cancers and healthy individuals, resulting in 95.7% sensitivity and 94.7% specificity. BladMetrix was furthermore evaluated in an independent prospective and blinded series of urine from patients with gross hematuria (n = 273), achieving 92.1% sensitivity, 93.3% specificity and a negative predictive value of 98.1%, with the potential to reduce the number of cystoscopies by 56.4%. Conclusions We here present BladMetrix, a novel DNA methylation urine test for non-invasive detection of bladder cancer, with high accuracy across tumor grades and stages, and the ability to spare a significant number of cystoscopies among patients with gross hematuria.

• Pinto, Rita; Hauge, Tobias; Jeanmougin, Marine; Pharo, Heidi Dietrichson; Kresse, Stine Henrichson & Honne, Hilde [Show all 13 contributors for this article] (2022). Targeted genetic and epigenetic profiling of esophageal adenocarcinomas and non-dysplastic Barrett’s esophagus. Clinical Epigenetics. 14(77), p. 1–11. doi: 10.1186/s13148-022-01287-7. Full text in Research Archive Show summary

  Background Despite the efforts to describe the molecular landscape of esophageal adenocarcinoma (EAC) and its precursor lesion Barrett’s esophagus (BE), discrepant findings are reported. Here, we investigated the prevalence of selected genetic (TP53 mutations and microsatellite instability (MSI) status) and epigenetic (DNA promoter hypermethylation of APC, CDKN2A, MGMT, TIMP3 and MLH1) modifications in a series of 19 non-dysplastic BE and 145 EAC samples. Additional biopsies from adjacent normal tissue were also evaluated. State-of-the-art methodologies and well-defined scoring criteria were applied in all molecular analyses. Results Overall, we confirmed frequent TP53 mutations among EAC (28%) in contrast to BE, which harbored no mutations. We demonstrated that MSI and MLH1 promoter hypermethylation are rare events, both in EAC and in BE. Our findings further support that APC, CDKN2A, MGMT and TIMP3 promoter hypermethylation is frequently seen in both lesions (21–89%), as well as in a subset of adjacent normal samples (up to 12%). Conclusions Our study further enlightens the molecular background of BE and EAC. To the best of our knowledge, this is one of the largest studies addressing a targeted analysis of genetic and epigenetic modifications simultaneously across a combined series of non-dysplastic BE and EAC samples.

• Vedeld, Hege Marie; Grimsrud, Marit Mæhle; Andresen, Kim; Pharo, Heidi Dietrichson; Seth, Erik von & Karlsen, Tom Hemming [Show all 15 contributors for this article] (2021). Early and accurate detection of cholangiocarcinoma in patients with primary sclerosing cholangitis by methylation markers in bile. Hepatology. ISSN 0270-9139. doi: 10.1002/hep.32125. Full text in Research Archive Show summary

  Background and Aims Primary sclerosing cholangitis (PSC) is associated with increased risk of cholangiocarcinoma (CCA). Early and accurate CCA detection represents an unmet clinical need as the majority of patients with PSC are diagnosed at an advanced stage of malignancy. In the present study, we aimed at establishing robust DNA methylation biomarkers in bile for early and accurate diagnosis of CCA in PSC. Approach and Results Droplet digital PCR (ddPCR) was used to analyze 344 bile samples from 273 patients with sporadic and PSC-associated CCA, PSC, and other nonmalignant liver diseases for promoter methylation of cysteine dioxygenase type 1, cannabinoid receptor interacting protein 1, septin 9, and vimentin. Receiver operating characteristic (ROC) curve analyses revealed high AUCs for all four markers (0.77–0.87) for CCA detection among patients with PSC. Including only samples from patients with PSC diagnosed with CCA ≤ 12 months following bile collection increased the accuracy for cancer detection, with a combined sensitivity of 100% (28/28) and a specificity of 90% (20/203). The specificity increased to 93% when only including patients with PSC with longtime follow-up (> 36 months) as controls, and remained high (83%) when only including patients with PSC and dysplasia as controls (n = 23). Importantly, the bile samples from the CCA-PSC ≤ 12 patients, all positive for the biomarkers, included both early-stage and late-stage CCA, different tumor growth patterns, anatomical locations, and carbohydrate antigen 19-9 levels. Conclusions Using highly sensitive ddPCR to analyze robust epigenetic biomarkers, CCA in PSC was accurately detected in bile, irrespective of clinical and molecular features, up to 12 months before CCA diagnosis. The findings suggest a potential for these biomarkers to complement current detection and screening methods for CCA in patients with PSC.

• Vedeld, Hege Marie; Folseraas, Trine & Lind, Guro Elisabeth (2020). Detecting cholangiocarcinoma in patients with primary sclerosing cholangitis – The promise of DNA methylation and molecular biomarkers. JHEP Reports. 2(5). doi: 10.1016/j.jhepr.2020.100143. Full text in Research Archive
• Flatin, Bjørnar Tovson Bae; Vedeld, Hege Marie; Pinto, Rita; Langerud, Jonas; Lind, Guro Elisabeth & Lothe, Ragnhild A [Show all 8 contributors for this article] (2020). Multiregional assessment of CIMP in primary colorectal cancers: Phenotype concordance but marker variability. International Journal of Cancer. ISSN 0020-7136. p. 1–6. doi: 10.1002/ijc.33425. Full text in Research Archive Show summary

  Intratumor heterogeneity of colorectal cancers (CRCs) is manifested both at the genomic and epigenomic levels. Early genetic aberrations in carcinogenesis are clonal and present throughout the tumors, but less is known about the heterogeneity of the epigenetic CpG island methylator phenotype (CIMP). CIMP characterizes a subgroup of CRCs thought to originate from specific precursor lesions, and it is defined by widespread DNA methylation within promoter regions. In this work, we investigated CIMP in two to four multiregional samples from 30 primary tumors (n = 86 samples) using the consensus Weisenberger gene panel (CACNA1G, IGF2, NEUROG1, RUNX3 and SOCS1). Twenty‐nine of 30 tumors (97%) showed concordant CIMP status in all samples, and percent methylated reference (PMR) values of all five markers had higher intertumor than intratumor variation (P value = 1.5e−09). However, a third of the CIMP+ tumors exhibited discrepancies in methylation status in at least one of the five gene markers. To conclude, CIMP status was consistent within primary CRCs, and it is likely a clonal phenotype. However, spatial discordances of the individual genes suggest that large‐scale analysis of multiregional samples could be of interest for identifying CIMP markers that are robust to intratumor heterogeneity.

• Jeanmougin, Marine; Håvik, Annette Bentsen; Cekaite, Lina; Brandal, Petter; Sveen, Anita & Meling, Torstein Ragnar [Show all 11 contributors for this article] (2020). Improved prognostication of glioblastoma beyond molecular subtyping by transcriptional profiling of the tumor microenvironment. Molecular Oncology. ISSN 1574-7891. p. 1016–1027. doi: 10.1002/1878-0261.12668. Full text in Research Archive Show summary

  Glioblastoma (GBM), the most aggressive form of brain cancer, is characterized by a high level of molecular heterogeneity, and infiltration by various immune and stromal cell populations. Important advances have been made in deciphering the microenvironment of GBMs, but its association with existing molecular subtypes and its potential prognostic role remain elusive. We have investigated the abundance of infiltrating immune and stromal cells in silico, from gene expression profiles. Two cohorts, including in‐house normal brain and glioma samples (n = 70) and a large sample set from TCGA (n = 393), were combined into a single exploratory dataset. A third independent cohort (n = 124) was used for validation. Tumors were clustered based on their microenvironment infiltration profiles, and associations with known GBM molecular subtypes and patient outcome were tested a posteriori in a multivariable setting. We identified a subset of GBM samples with significantly higher abundances of most immune and stromal cell populations. This subset showed increased expression of both immune suppressor and immune effector genes compared to other GBMs and was enriched for the mesenchymal molecular subtype. Survival analyses suggested that tumor microenvironment infiltration pattern was an independent prognostic factor for GBM patients. Among all, patients with the mesenchymal subtype with low immune and stromal infiltration had the poorest survival. By combining molecular subtyping with gene expression measures of tumor infiltration, the present work contributes with improving prognostic models in GBM.

• Larsen, Louise Katrine; Lind, Guro Elisabeth; Guldberg, Per & Dahl, Christina (2019). DNA-methylation-based detection of urological cancer in urine: Overview of biomarkers and considerations on biomarker design, source of DNA, and detection technologies. International Journal of Molecular Sciences. ISSN 1661-6596. 20:2657(11), p. 1–20. doi: 10.3390/ijms20112657. Full text in Research Archive
• Marcuello, María; Vymetalkova, Veronika; Neves, Rui P.L.; Duran-Sanchon, Saray; Vedeld, Hege Marie & Tham, Emma [Show all 16 contributors for this article] (2019). Circulating biomarkers for early detection and clinical management of colorectal cancer. Molecular Aspects of Medicine. ISSN 0098-2997. p. 1–16. doi: 10.1016/j.mam.2019.06.002. Full text in Research Archive
• Pinto, Diana; Pinto, Carla; Guerra, Joana; Pinheiro, Manuela; Santos, Rui & Vedeld, Hege Marie [Show all 15 contributors for this article] (2018). Contribution of MLH1 constitutional methylation for Lynch syndrome diagnosis in patients with tumor MLH1 downregulation. Cancer Medicine. 7(2), p. 433–444. doi: 10.1002/cam4.1285. Full text in Research Archive Show summary

  Constitutional epimutation of the two major mismatch repair genes, MLH1 and MSH2, has been identified as an alternative mechanism that predisposes to the development of Lynch syndrome. In the present work, we aimed to investigate the prevalence of MLH1 constitutional methylation in colorectal cancer (CRC) patients with abnormal expression of the MLH1 protein in their tumors. In a series of 38 patients who met clinical criteria for Lynch syndrome genetic testing, with loss of MLH1 expression in the tumor and with no germline mutations in the MLH1 gene (35/38) or with tumors presenting the BRAF p.Val600Glu mutation (3/38), we screened for constitutional methylation of the MLH1 gene promoter using methylation‐specific multiplex ligation‐dependent probe amplification (MS‐MLPA) in various biological samples. We found four (4/38; 10.5%) patients with constitutional methylation in the MLH1 gene promoter. RNA studies demonstrated decreased MLH1 expression in the cases with constitutional methylation when compared with controls. We could infer the mosaic nature of MLH1 constitutional hypermethylation in tissues originated from different embryonic germ layers, and in one family we could show that it occurred de novo. We conclude that constitutional MLH1 methylation occurs in a significant proportion of patients who have loss of MLH1 protein expression in their tumors and no MLH1 pathogenic germline mutation. Furthermore, we provide evidence that MLH1 constitutional hypermethylation is the molecular mechanism behind about 3% of Lynch syndrome families diagnosed in our institution, especially in patients with early onset or multiple primary tumors without significant family history.

• Pharo, Heidi Dietrichson; Andresen, Kim; Berg, Kaja Christine Graue; Lothe, Ragnhild A; Jeanmougin, Marine & Lind, Guro Elisabeth (2018). A robust internal control for high-precision DNA methylation analyses by droplet digital PCR. Clinical Epigenetics. 10(24). doi: 10.1186/s13148-018-0456-5. Full text in Research Archive Show summary

  Background Droplet digital PCR (ddPCR) allows absolute quantification of nucleic acids and has potential for improved non-invasive detection of DNA methylation. For increased precision of the methylation analysis, we aimed to develop a robust internal control for use in methylation-specific ddPCR. Methods Two control design approaches were tested: (a) targeting a genomic region shared across members of a gene family and (b) combining multiple assays targeting different pericentromeric loci on different chromosomes. Through analyses of 34 colorectal cancer cell lines, the performance of the control assay candidates was optimized and evaluated, both individually and in various combinations, using the QX200™ droplet digital PCR platform (Bio-Rad). The best-performing control was tested in combination with assays targeting methylated CDO1, SEPT9, and VIM. Results A 4Plex panel consisting of EPHA3, KBTBD4, PLEKHF1, and SYT10 was identified as the best-performing control. The use of the 4Plex for normalization reduced the variability in methylation values, corrected for differences in template amount, and diminished the effect of chromosomal aberrations. Positive Droplet Calling (PoDCall), an R-based algorithm for standardized threshold determination, was developed, ensuring consistency of the ddPCR results. Conclusion Implementation of a robust internal control, i.e., the 4Plex, and an algorithm for automated threshold determination, PoDCall, in methylation-specific ddPCR increase the precision of DNA methylation analysis.

• Vedeld, Hege Marie; Nesbakken, Arild; Lothe, Ragnhild A & Lind, Guro Elisabeth (2018). Re-assessing ZNF331 as a DNA methylation biomarker for colorectal cancer. Clinical Epigenetics. 10(1). doi: 10.1186/s13148-018-0503-2. Full text in Research Archive Show summary

  We have previously shown that aberrant promoter methylation of ZNF331 is a potential biomarker for colorectal cancer detection with high sensitivity (71%) and specificity (98%). This finding was recently confirmed by others, and it was additionally suggested that promoter methylation of ZNF331 was an independent prognostic biomarker for colorectal cancer (n = 146). In the current study, our initial colorectal cancer sample series was extended to include a total of 423 cancer tissue samples. Aberrant promoter methylation was found in 71% of the samples, thus repeatedly suggesting the biomarker potential of ZNF331 for detection of colorectal cancer. Furthermore, multivariate Cox’s analysis indicated a trend towards inferior overall survival for colorectal cancer patients with aberrant methylation of ZNF331.

• Berg, Kaja Christine Graue; Eide, Peter Andreas Wold; Eilertsen, Ina Andrassy; Johannessen, Bjarne; Bruun, Jarle & Danielsen, Stine Aske [Show all 14 contributors for this article] (2017). Multi-omics of 34 colorectal cancer cell lines - a resource for biomedical studies. Molecular Cancer. 16:116, p. 1–16. doi: 10.1186/s12943-017-0691-y. Full text in Research Archive
• Vedeld, Hege Marie; Goel, Ajay & Lind, Guro Elisabeth (2017). Epigenetic biomarkers in gastrointestinal cancers: The current state and clinical perspectives. Seminars in Cancer Biology. ISSN 1044-579X. 51, p. 36–49. doi: 10.1016/j.semcancer.2017.12.004. Full text in Research Archive
• Sveen, Anita; Johannessen, Bjarne; Tengs, Torstein; Danielsen, Stine Aske; Eilertsen, Ina Andrassy & Lind, Guro Elisabeth [Show all 16 contributors for this article] (2017). Multilevel genomics of colorectal cancers with microsatellite instability – clinical impact of JAK1 mutations and consensus molecular subtype 1. Genome Medicine. 9(1). doi: 10.1186/s13073-017-0434-0. Full text in Research Archive Show summary

  Background Approximately 15% of primary colorectal cancers have DNA mismatch repair deficiency, causing a complex genome with thousands of small mutations—the microsatellite instability (MSI) phenotype. We investigated molecular heterogeneity and tumor immunogenicity in relation to clinical endpoints within this distinct subtype of colorectal cancers. Methods A total of 333 primary MSI+ colorectal tumors from multiple cohorts were analyzed by multilevel genomics and computational modeling—including mutation profiling, clonality modeling, and neoantigen prediction in a subset of the tumors, as well as gene expression profiling for consensus molecular subtypes (CMS) and immune cell infiltration. Results Novel, frequent frameshift mutations in four cancer-critical genes were identified by deep exome sequencing, including in CRTC1, BCL9, JAK1, and PTCH1. JAK1 loss-of-function mutations were validated with an overall frequency of 20% in Norwegian and British patients, and mutated tumors had up-regulation of transcriptional signatures associated with resistance to anti-PD-1 treatment. Clonality analyses revealed a high level of intra-tumor heterogeneity; however, this was not associated with disease progression. Among the MSI+ tumors, the total mutation load correlated with the number of predicted neoantigens (P = 4 × 10−5), but not with immune cell infiltration—this was dependent on the CMS class; MSI+ tumors in CMS1 were highly immunogenic compared to MSI+ tumors in CMS2-4. Both JAK1 mutations and CMS1 were favorable prognostic factors (hazard ratios 0.2 [0.05–0.9] and 0.4 [0.2–0.9], respectively, P = 0.03 and 0.02). Conclusions Multilevel genomic analyses of MSI+ colorectal cancer revealed molecular heterogeneity with clinical relevance, including tumor immunogenicity and a favorable patient outcome associated with JAK1 mutations and the transcriptomic subgroup CMS1, emphasizing the potential for prognostic stratification of this clinically important subtype. See related research highlight by Samstein and Chan 10.1186/s13073-017-0438-9

• Lind, Guro Elisabeth; Guriby, Marianne; Ahlquist, Terje Cruickshank; Hussain, Israr; Jeanmougin, Marine & Søreide, Kjetil [Show all 9 contributors for this article] (2017). Prognostic relevance of an epigenetic biomarker panel in sentinel lymph nodes from colon cancer patients. Clinical Epigenetics. 9:97, p. 1–8. doi: 10.1186/s13148-017-0397-4. Full text in Research Archive Show summary

  Background: Patients with early colorectal cancer (stages I–II) generally have a good prognosis, but a subgroup of 15–20% experiences relapse and eventually die of disease. Occult metastases have been suggested as a marker for increased risk of recurrence in patients with node-negative disease. Using a previously identified, highly accurate epigenetic biomarker panel for early detection of colorectal tumors, we aimed at evaluating the prognostic value of occult metastases in sentinel lymph nodes of colon cancer patients. Results: The biomarker panel was analyzed by quantitative methylation-specific PCR in primary tumors and 783 sentinel lymph nodes from 201 patients. The panel status in sentinel lymph nodes showed a strong association with lymph node stage (P = 8.2E−17). Compared with routine lymph node diagnostics, the biomarker panel had a sensitivity of 79% (31/39). Interestingly, among 162 patients with negative lymph nodes from routine diagnostics, 13 (8%) were positive for the biomarker panel. Colon cancer patients with high sentinel lymph node methylation had an inferior prognosis (5-year overall survival P = 3.0E−4; time to recurrence P = 3.1E−4), although not significant. The same trend was observed in multivariate analyses (P = 1.4E−1 and P = 6.7E−2, respectively). Occult sentinel lymph node metastases were not detected in early stage (I–II) colon cancer patients who experienced relapse. Conclusions: Colon cancer patients with high sentinel lymph node methylation of the analyzed epigenetic biomarker panel had an inferior prognosis, although not significant in multivariate analyses. Occult metastases in TNM stage II patients that experienced relapse were not detected.

• Vedeld, Hege Marie; Merok, Marianne Aarstad; Jeanmougin, Marine; Danielsen, Stine Aske; Honne, Hilde & Presthus, Gro [Show all 13 contributors for this article] (2017). CpG island methylator phenotype identifies high risk patients among microsatellite stable BRAF mutated colorectal cancers. International Journal of Cancer. ISSN 0020-7136. 141(5), p. 967–976. doi: 10.1002/ijc.30796. Full text in Research Archive
• Banales, Jesus M.; Cardinale, Vincenzo; Carpino, Guido; Marzioni, Marco; Andersen, Jesper B. & Invernizzi, Pietro [Show all 24 contributors for this article] (2016). Expert consensus document: Cholangiocarcinoma: current knowledge and future perspectives consensus statement from the European Network for the Study of Cholangiocarcinoma (ENS-CCA). Nature reviews: Gastroenterology & hepatology. ISSN 1759-5045. 13(5), p. 261–280. doi: 10.1038/nrgastro.2016.51. Full text in Research Archive
• Pharo, Heidi Dietrichson; Honne, Hilde; Vedeld, Hege Marie; Dahl, Christina; Andresen, Kim & Liestøl, Knut [Show all 9 contributors for this article] (2016). Experimental factors affecting the robustness of DNA methylation analysis. Scientific Reports. 6. doi: 10.1038/srep33936. Full text in Research Archive
• Kolberg, Matthias; Høland, Maren; Lind, Guro Elisabeth; Ågesen, Trude Holmeide; Skotheim, Rolf Inge & Hall, Kirsten Sundby [Show all 11 contributors for this article] (2015). Protein expression of BIRC5, TK1, and TOP2A in malignant peripheral nerve sheath tumours - A prognostic test after surgical resection. Molecular Oncology. ISSN 1574-7891. 9(6), p. 1129–1139. doi: 10.1016/j.molonc.2015.02.005. Full text in Research Archive
• Cekaite, Lina; Eide, Peter Andreas Wold; Lind, Guro Elisabeth; Skotheim, Rolf I. & Lothe, Ragnhild A (2015). MicroRNAs as growth regulators, their function and biomarker status in colorectal cancer. OncoTarget. 7(6), p. 6476–6505. doi: 10.18632/oncotarget.6390. Full text in Research Archive
• Andresen, Kim; Boberg, Kirsten Muri; Vedeld, Hege Marie; Honne, Hilde; Jebsen, Peter Wilhelm & Hektoen, Merete [Show all 16 contributors for this article] (2015). Four DNA methylation biomarkers in biliary brush samples accurately identify the presence of cholangiocarcinoma. Hepatology. ISSN 0270-9139. 61(5), p. 1651–1659. doi: 10.1002/hep.27707. Full text in Research Archive
• Bruun, Jarle; Kolberg, Matthias; Ahlquist, Terje Cruickshank; Røyrvik, Ellen Christine; Nome, Torfinn & Leithe, Edward [Show all 18 contributors for this article] (2015). Regulator of chromosome condensation 2 identifies high-risk patients within both major phenotypes of colorectal cancer. Clinical Cancer Research. ISSN 1078-0432. 21(16), p. 3759–3770. doi: 10.1158/1078-0432.CCR-14-3294. Full text in Research Archive
• Danielsen, Stine Aske; Lind, Guro Elisabeth; Kolberg, Matthias; Høland, Maren; Bjerkehagen, Bodil & Hall, Kirsten Sundby [Show all 11 contributors for this article] (2015). Methylated RASSF1A in malignant peripheral nerve sheath tumors identifies neurofibromatosis type 1 patients with inferior prognosis. Neuro-Oncology. ISSN 1522-8517. 17(1), p. 63–69. doi: 10.1093/neuonc/nou140. Full text in Research Archive
• Sirnes, Solveig; Lind, Guro Elisabeth; Bruun, Jarle; Fykerud, Tone Aase; Mesnil, Marc & Lothe, Ragnhild A [Show all 9 contributors for this article] (2015). Connexins in colorectal cancer pathogenesis. International Journal of Cancer. ISSN 0020-7136. 137(1), p. 1–11. doi: 10.1002/ijc.28911. Full text in Research Archive
• Vedeld, Hege Marie; Skotheim, Rolf Inge; Lothe, Ragnhild A & Lind, Guro Elisabeth (2014). The recently suggested intestinal cancer stem cell marker DCLK1 is an epigenetic biomarker for colorectal cancer. Epigenetics. ISSN 1559-2294. 9(3), p. 346–350. doi: 10.4161/epi.27582. Full text in Research Archive
• Almeida, Mafalda; Costa, Vera L; Costa, Natália R.; Ramalho-Carvalho, João; Baptista, Tiago & Ribeiro, Franclim R [Show all 13 contributors for this article] (2014). Epigenetic regulation of EFEMP1 in prostate cancer: biological relevance and clinical potential. Journal of Cellular and Molecular Medicine. ISSN 1582-1838. 18(11), p. 2287–2297. doi: 10.1111/jcmm.12394. Full text in Research Archive
• Bethge, Nicole; Honne, Hilde; Andresen, Kim; Hilden, Vera Irene; Trøen, Gunhild & Liestøl, Knut [Show all 10 contributors for this article] (2014). A gene panel, including LRP12, is frequently hypermethylated in major types of B-cell lymphoma. PLOS ONE. 9(9). doi: 10.1371/journal.pone.0104249. Full text in Research Archive
• Bethge, Nicole; Lothe, Ragnhild A; Honne, Hilde; Andresen, Kim; Trøen, Gunhild & Eknæs, Mette [Show all 11 contributors for this article] (2014). Colorectal cancer DNA methylation marker panel validated with high performance in Non-Hodgkin lymphoma. Epigenetics. ISSN 1559-2294. 9(3), p. 428–436. doi: 10.4161/epi.27554. Full text in Research Archive
• Vedeld, Hege Marie; Andresen, Kim; Eilertsen, Ina Andrassy; Nesbakken, Arild; Seruca, Raquel & Gladhaug, Ivar Prydz [Show all 10 contributors for this article] (2014). The novel colorectal cancer biomarkers CDO1, ZSCAN18 and ZNF331 are frequently methylated across gastrointestinal cancers. International Journal of Cancer. ISSN 0020-7136. 136(4), p. 844–853. doi: 10.1002/ijc.29039. Full text in Research Archive
• Bethge, Nicole; Honne, Hilde; Hilden, Vera Irene; Trøen, Gunhild; Eknæs, Mette & Liestøl, Knut [Show all 10 contributors for this article] (2013). Identification of Highly Methylated Genes across Various Types of B-Cell Non-Hodgkin Lymphoma. PLOS ONE. 8(11). doi: 10.1371/journal.pone.0079602. Full text in Research Archive
• Mesquita, Barbara; Lopes, Paula; Rodrigues, Ana; Pereira, Deolinda; Afonso, Mariana & Leal, Conceicao [Show all 11 contributors for this article] (2013). Frequent copy number gains at 1q21 and 1q32 are associated with overexpression of the ETS transcription factors ETV3 and ELF3 in breast cancer irrespective of molecular subtypes. Breast Cancer Research and Treatment. ISSN 0167-6806. 138(1), p. 37–45. doi: 10.1007/s10549-013-2408-2. Full text in Research Archive
• Nome, Torfinn; Thomassen, Gard O Sundby; Bruun, Jarle; Ahlquist, Terje Cruickshank; Bakken, Anne Cathrine & Hoff, Andreas Midbøe [Show all 17 contributors for this article] (2013). Common fusion transcripts identified in colorectal cancer cell lines by high throughput RNA sequencing. Translational Oncology. ISSN 1944-7124. 6(5), p. 546–553. doi: 10.1593/tlo.13457. Full text in Research Archive
• Ali, Deeqa Ahmed Mohamed; Eide, Peter Andreas Wold; Eilertsen, Ina Andrassy; Danielsen, Stine Aske; Eknæs, Mette & Hektoen, Merete [Show all 8 contributors for this article] (2013). Epigenetic and genetic features of 24 colon cancer cell lines. Oncogenesis. 2. doi: 10.1038/oncsis.2013.35. Full text in Research Archive
• Sveen, Anita; Bakken, Anne Cathrine; Ågesen, Trude Holmeide; Lind, Guro Elisabeth; Nesbakken, Arild & Nordgård, Oddmund [Show all 10 contributors for this article] (2012). The exon-level biomarker SLC39A14 has organ-confined cancer-specificity in colorectal cancer. International Journal of Cancer. ISSN 0020-7136. 131(6), p. 1479–1485. doi: 10.1002/ijc.27399. Full text in Research Archive
• Paulo, Paula; Barros-Silva, Joao D.; Ribeiro, Franclim R; Ramalho-Carvalho, Joao; Jeronimo, Carmen & Henrique, Rui [Show all 10 contributors for this article] (2012). FLI1 is a novel ETS transcription factor involved in gene fusions in prostate cancer. Genes, Chromosomes and Cancer. ISSN 1045-2257. 51(3), p. 240–249. doi: 10.1002/gcc.20948. Full text in Research Archive
• Cekaite, Lina; Rantala, Juha K.; Bruun, Jarle; Guriby, Marianne; Ågesen, Trude Holmeide & Danielsen, Stine Aske [Show all 11 contributors for this article] (2012). MiR-9,-31, and-182 Deregulation Promote Proliferation and Tumor Cell Survival in Colon Cancer. Neoplasia. ISSN 1522-8002. 14(9), p. 868–U126. doi: 10.1593/neo.121094. Full text in Research Archive
• Andresen, Kim; Boberg, Kirsten Muri; Vedeld, Hege Marie; Honne, Hilde; Hektoen, Merete & Wadsworth, Christopher A [Show all 13 contributors for this article] (2012). Novel target genes and a valid biomarker panel identified for cholangiocarcinoma. Epigenetics. ISSN 1559-2294. 7(11), p. 1249–1257. doi: 10.4161/epi.22191. Full text in Research Archive
• Håvik, Annette Bentsen; Brandal, Petter; Honne, Hilde; Dahlback, Hanne-Sofie Spenning; Scheie, David & Hektoen, Merete [Show all 11 contributors for this article] (2012). MGMT promoter methylation in gliomas-assessment by pyrosequencing and quantitative methylation-specific PCR. Journal of Translational Medicine. 10. doi: 10.1186/1479-5876-10-36. Full text in Research Archive Show summary

  Background Methylation of the O6-methylguanine-DNA methyltransferase (MGMT) gene promoter is a favorable prognostic factor in glioblastoma patients. However, reported methylation frequencies vary significantly partly due to lack of consensus in the choice of analytical method. Method We examined 35 low- and 99 high-grade gliomas using quantitative methylation specific PCR (qMSP) and pyrosequencing. Gene expression level of MGMT was analyzed by RT-PCR. Results When examined by qMSP, 26% of low-grade and 37% of high-grade gliomas were found to be methylated, whereas 97% of low-grade and 55% of high-grade gliomas were found methylated by pyrosequencing. The average MGMT gene expression level was significantly lower in the group of patients with a methylated promoter independent of method used for methylation detection. Primary glioblastoma patients with a methylated MGMT promoter (as evaluated by both methylation detection methods) had approximately 5 months longer median survival compared to patients with an unmethylated promoter (log-rank test; pyrosequencing P = .02, qMSP P = .06). One third of the analyzed samples had conflicting methylation results when comparing the data from the qMSP and pyrosequencing. The overall survival analysis shows that these patients have an intermediate prognosis between the groups with concordant MGMT promoter methylation results when comparing the two methods. Conclusion In our opinion, MGMT promoter methylation analysis gives sufficient prognostic information to merit its inclusion in the standard management of patients with high-grade gliomas, and in this study pyrosequencing came across as the better analytical method.

• Ågesen, Trude Holmeide; Sveen, Anita; Merok, Marianne Aarstad; Lind, Guro Elisabeth; Nesbakken, Arild & Skotheim, Rolf Inge [Show all 7 contributors for this article] (2012). ColoGuideEx: a robust gene classifier specific for stage II colorectal cancer prognosis. Gut. ISSN 0017-5749. 61(11), p. 1560–1567. doi: 10.1136/gutjnl-2011-301179. Full text in Research Archive
• Ahmed, Deeqa; Danielsen, Stine Aske; Ågesen, Trude Holmeide; Bretthauer, Michael; Thiis-Evensen, Espen & Hoff, Geir [Show all 10 contributors for this article] (2012). A tissue-based comparative effectiveness analysis of biomarkers for early detection of colorectal tumors. Clinical and Translational Gastroenterology. 3. doi: 10.1038/ctg.2012.21. Full text in Research Archive
• Sirnes, Solveig; Bruun, Jarle; Kolberg, Matthias; Kjenseth, Ane Hansen; Lind, Guro Elisabeth & Svindland, Aud [Show all 11 contributors for this article] (2012). Connexin43 acts as a colorectal cancer tumor suppressor and predicts disease outcome. International Journal of Cancer. ISSN 0020-7136. 131(3), p. 570–581. doi: 10.1002/ijc.26392. Full text in Research Archive
• Lind, Guro Elisabeth; Raiborg, Camilla; Danielsen, Stine Aske; Rognum, Torleiv Ole; Thiis-Evensen, Espen & Hoff, Geir [Show all 9 contributors for this article] (2011). SPG20, a novel biomarker for early detection of colorectal cancer, encodes a regulator of cytokinesis. Oncogene. ISSN 0950-9232. 30(37), p. 3967–3978. doi: 10.1038/onc.2011.109. Full text in Research Archive
• Costa, Vera L.; Henrique, Rui; Danielsen, Stine Aske; Eknæs, Mette; Patrcio, Patricia & Morais, Antonio [Show all 11 contributors for this article] (2011). TCF21 and PCDH17 methylation An innovative panel of biomarkers for a simultaneous detection of urological cancers. Epigenetics. ISSN 1559-2294. 6(9), p. 1120–1130. doi: 10.4161/epi.6.9.16376. Full text in Research Archive
• Ribeiro, Franclim R; Paulo, Paula; Costa, Vera L; Barros-Silva, Joao D.; Ramalho-Carvalho, Joao & Jeronimo, Carmen [Show all 11 contributors for this article] (2011). Cysteine-Rich Secretory Protein-3 (CRISP3) Is Strongly Up-Regulated in Prostate Carcinomas with the TMPRSS2-ERG Fusion Gene. PLOS ONE. 6(7), p. e22317–e22317. doi: 10.1371/journal.pone.0022317. Full text in Research Archive
• Boberg, Kirsten Muri & Lind, Guro Elisabeth (2011). Primary sclerosing cholangitis and malignancy. Baillière's Best Practice & Research Clinical Gastroenterology. ISSN 1521-6918. 25(6), p. 753–764. doi: 10.1016/j.bpg.2011.10.002. Full text in Research Archive
• Lind, Guro Elisabeth; Danielsen, Stine Aske; Ahlquist, Terje Cruickshank; Merok, Marianne Aarstad; Andresen, Kim & Skotheim, Rolf Inge [Show all 14 contributors for this article] (2011). Identification of an epigenetic biomarker panel with high sensitivity and specificity for colorectal cancer and adenomas. Molecular Cancer. 10. doi: 10.1186/1476-4598-10-85. Full text in Research Archive Show summary

  Background The presence of cancer-specific DNA methylation patterns in epithelial colorectal cells in human feces provides the prospect of a simple, non-invasive screening test for colorectal cancer and its precursor, the adenoma. This study investigates a panel of epigenetic markers for the detection of colorectal cancer and adenomas. Methods Candidate biomarkers were subjected to quantitative methylation analysis in test sets of tissue samples from colorectal cancers, adenomas, and normal colonic mucosa. All findings were verified in independent clinical validation series. A total of 523 human samples were included in the study. Receiver operating characteristic (ROC) curve analysis was used to evaluate the performance of the biomarker panel. Results Promoter hypermethylation of the genes CNRIP1, FBN1, INA, MAL, SNCA, and SPG20 was frequent in both colorectal cancers (65-94%) and adenomas (35-91%), whereas normal mucosa samples were rarely (0-5%) methylated. The combined sensitivity of at least two positives among the six markers was 94% for colorectal cancers and 93% for adenoma samples, with a specificity of 98%. The resulting areas under the ROC curve were 0.984 for cancers and 0.968 for adenomas versus normal mucosa. Conclusions The novel epigenetic marker panel shows very high sensitivity and specificity for both colorectal cancers and adenomas. Our findings suggest this biomarker panel to be highly suitable for early tumor detection.

• Sirnes, Solveig; Honne, Hilde; Danielsen, Stine Aske; Ali, Deeqa Ahmed Mohamed; Rognum, Torleiv Ole & Meling, Gunn Iren [Show all 10 contributors for this article] (2011). DNA methylation analyses of the connexin gene family reveal silencing of GJC1 (Connexin45) by promoter hypermethylation in colorectal cancer. Epigenetics. ISSN 1559-2294. 6(5), p. 602–609. doi: 10.4161/epi.6.5.15237. Full text in Research Archive
• Danielsen, Stine Aske; Cekaite, Lina; Ågesen, Trude Holmeide; Sveen, Anita; Nesbakken, Arild & Thiis-Evensen, Espen [Show all 9 contributors for this article] (2011). Phospholipase C Isozymes Are Deregulated in Colorectal Cancer - Insights Gained from Gene Set Enrichment Analysis of the Transcriptome. PLOS ONE. 6(9). doi: 10.1371/journal.pone.0024419. Full text in Research Archive
• Alagaratnam, Sharmini; Lind, Guro Elisabeth; Kraggerud, Sigrid M.; Lothe, Ragnhild A & Skotheim, Rolf Inge (2011). The testicular germ cell tumour transcriptome. International Journal of Andrology. ISSN 0105-6263. 34(4pt2), p. e133–e151. doi: 10.1111/j.1365-2605.2011.01169.x. Full text in Research Archive
• Ali, Deeqa Ahmed Mohamed; Lothe, Ragnhild A; Rivedal, Edgar & Lind, Guro Elisabeth (2011). Quantitative validation of GJC1 promoter hypermethylation in benign and malignant colorectal tumors. Endocrine-Related Cancer. ISSN 1351-0088. 18(6), p. C31–C34. doi: 10.1530/ERC-11-0204. Full text in Research Archive
• Ågesen, Trude Holmeide; Berg, Marianne; Clancy, Trevor; Thiis-Evensen, Espen; Cekaite, Lina & Lind, Guro Elisabeth [Show all 16 contributors for this article] (2011). CLC and IFNAR1 are differentially expressed and a global immunity score is distinct between early- and late-onset colorectal cancer. Genes and Immunity. ISSN 1466-4879. 12(8), p. 653–662. doi: 10.1038/gene.2011.43. Full text in Research Archive
• Løvf, Marthe; Thomassen, Gard O Sundby; Bakken, Anne Cathrine; Celestino, Ricardo; Fioretos, Thoas & Lind, Guro Elisabeth [Show all 8 contributors for this article] (2011). Fusion Gene Microarray Reveals Cancer Type-Specificity Among Fusion Genes. Genes, Chromosomes and Cancer. ISSN 1045-2257. 50(5), p. 348–357. doi: 10.1002/gcc.20860. Full text in Research Archive
• Brekke, Helge Roar; Ribeiro, Franclim R; Kolberg, Matthias; Ågesen, Trude H.; Lind, Guro Elisabeth & Eknæs, Mette [Show all 15 contributors for this article] (2010). Genomic Changes in Chromosomes 10, 16, and X in Malignant Peripheral Nerve Sheath Tumors Identify a High-Risk Patient Group. Journal of Clinical Oncology. ISSN 0732-183X. 28(9), p. 1573–1582. doi: 10.1200/JCO.2009.24.8989. Full text in Research Archive
• Costa, Vera L; Henrique, Rui; Danielsen, Stine Aske; Duarte-Pereira, S; Eknæs, Mette & Skotheim, Rolf Inge [Show all 13 contributors for this article] (2010). Three Epigenetic Biomarkers, GDF15, TMEFF2, and VIM, Accurately Predict Bladder Cancer from DNA-Based Analyses of Urine Samples. Clinical Cancer Research. ISSN 1078-0432. 16(23), p. 5842–5851. doi: 10.1158/1078-0432.CCR-10-1312. Full text in Research Archive
• Pinheiro, M; Ahlquist, Terje Cruickshank; Danielsen, Stine Aske; Lind, Guro Elisabeth; Veiga, I & Pinto, C [Show all 16 contributors for this article] (2010). Colorectal carcinomas with microsatellite instability display a different pattern of target gene mutations according to large bowel site of origin. BMC Cancer. 10. doi: 10.1186/1471-2407-10-587. Full text in Research Archive
• Zwierzina, Heinz; Bardelli, Alberto; Ciardiello, Fortunato; Gariboldi, Manuela; Håkansson, Leif & Lambrechts, Diether [Show all 12 contributors for this article] (2010). Molecularly targeted therapies for colorectal cancer: Strategies for implementing translational research in clinical trials. Current opinion in molecular therapeutics (Print). ISSN 1464-8431. 12(6), p. 703–711. Full text in Research Archive
• Skotheim, Rolf Inge; Thomassen, Gard O Sundby; Eken, Marthe; Lind, Guro Elisabeth; Micci, Francesca & Ribeiro, FR [Show all 11 contributors for this article] (2009). A universal assay for detection of oncogenic fusion transcripts by oligo microarray analysis. Molecular Cancer. 8. doi: 10.1186/1476-4598-8-5. Full text in Research Archive Show summary

  Background The ability to detect neoplasia-specific fusion genes is important not only in cancer research, but also increasingly in clinical settings to ensure that correct diagnosis is made and the optimal treatment is chosen. However, the available methodologies to detect such fusions all have their distinct short-comings. Results We describe a novel oligonucleotide microarray strategy whereby one can screen for all known oncogenic fusion transcripts in a single experiment. To accomplish this, we combine measurements of chimeric transcript junctions with exon-wise measurements of individual fusion partners. To demonstrate the usefulness of the approach, we designed a DNA microarray containing 68,861 oligonucleotide probes that includes oligos covering all combinations of chimeric exon-exon junctions from 275 pairs of fusion genes, as well as sets of oligos internal to all the exons of the fusion partners. Using this array, proof of principle was demonstrated by detection of known fusion genes (such as TCF3:PBX1, ETV6:RUNX1, and TMPRSS2:ERG) from all six positive controls consisting of leukemia cell lines and prostate cancer biopsies. Conclusion This new method bears promise of an important complement to currently used diagnostic and research tools for the detection of fusion genes in neoplastic diseases.

• Ahlquist, Terje Cruickshank; Bottillo, Irene; Danielsen, Stine Aske; Meling, Gunn Iren; Rognum, Torleiv Ole & Lind, Gruo Elisabeth [Show all 8 contributors for this article] (2008). RAS Signaling in Colorectal Carcinomas through Alterations of RAS, RAF, NF1, and/or RASSF1A. Neoplasia. ISSN 1522-8002. 10(7), p. 680–686. doi: 10.1593/neo.08312. Full text in Research Archive
• Danielsen, Stine Aske; Lind, Gruo Elisabeth; Bjørnslett, Merete Pauline; Meling, Gunn Iren; Rognum, Torleiv Ole & Heim, Sverre [Show all 7 contributors for this article] (2008). Novel Mutations of the Suppressor GEne PTEN in Colorectal Carcinomas Stratified by Microsatellite Instability- and TP53 Mutation-Status. Human Mutation. ISSN 1059-7794. 29(11), p. E252–E262. doi: 10.1002/humu.20860. Full text in Research Archive
• Lind, Gruo Elisabeth; Ahlquist, Terje Cruickshank; Kolberg, Matthias; Berg, Marianne; Lier, Mette Eknæs & Alonso, MA [Show all 12 contributors for this article] (2008). Hypermethylated MAL gene - a silent marker of early colon tumorigenesis. Journal of Translational Medicine. 6, p. 13–13. doi: 10.1186/1479-5876-6-13. Full text in Research Archive Show summary

  Background Tumor-derived aberrantly methylated DNA might serve as diagnostic biomarkers for cancer, but so far, few such markers have been identified. The aim of the present study was to investigate the potential of the MAL (T-cell differentiation protein) gene as an early epigenetic diagnostic marker for colorectal tumors. Methods Using methylation-specific polymerase chain reaction (MSP) the promoter methylation status of MAL was analyzed in 218 samples, including normal mucosa (n = 44), colorectal adenomas (n = 63), carcinomas (n = 65), and various cancer cell lines (n = 46). Direct bisulphite sequencing was performed to confirm the MSP results. MAL gene expression was investigated with real time quantitative analyses before and after epigenetic drug treatment. Immunohistochemical analysis of MAL was done using normal colon mucosa samples (n = 5) and a tissue microarray with 292 colorectal tumors. Results Bisulphite sequencing revealed that the methylation was unequally distributed within the MAL promoter and by MSP analysis a region close to the transcription start point was shown to be hypermethylated in the majority of colorectal carcinomas (49/61, 80%) as well as in adenomas (45/63, 71%). In contrast, only a minority of the normal mucosa samples displayed hypermethylation (1/23, 4%). The hypermethylation of MAL was significantly associated with reduced or lost gene expression in in vitro models. Furthermore, removal of the methylation re-induced gene expression in colon cancer cell lines. Finally, MAL protein was expressed in epithelial cells of normal colon mucosa, but not in the malignant cells of the same type. Conclusion Promoter hypermethylation of MAL was present in the vast majority of benign and malignant colorectal tumors, and only rarely in normal mucosa, which makes it suitable as a diagnostic marker for early colorectal tumorigenesis.

• Ahlquist, Terje Cruickshank; Lind, Guro Elisabeth; Costa, Vera L; Meling, Gunn Iren; Vatn, Morten H & Hoff, Geir S [Show all 10 contributors for this article] (2008). Gene methylation profiles of normal mucosa, and benign and malignant colorectal tumors identify early onset markers. Molecular Cancer. 7. doi: 10.1186/1476-4598-7-94. Full text in Research Archive Show summary

  Background Multiple epigenetic and genetic changes have been reported in colorectal tumors, but few of these have clinical impact. This study aims to pinpoint epigenetic markers that can discriminate between non-malignant and malignant tissue from the large bowel, i.e. markers with diagnostic potential. The methylation status of eleven genes (ADAMTS1, CDKN2A, CRABP1, HOXA9, MAL, MGMT, MLH1, NR3C1, PTEN, RUNX3, and SCGB3A1) was determined in 154 tissue samples including normal mucosa, adenomas, and carcinomas of the colorectum. The gene-specific and widespread methylation status among the carcinomas was related to patient gender and age, and microsatellite instability status. Possible CIMP tumors were identified by comparing the methylation profile with microsatellite instability (MSI), BRAF-, KRAS-, and TP53 mutation status. Results The mean number of methylated genes per sample was 0.4 in normal colon mucosa from tumor-free individuals, 1.2 in mucosa from cancerous bowels, 2.2 in adenomas, and 3.9 in carcinomas. Widespread methylation was found in both adenomas and carcinomas. The promoters of ADAMTS1, MAL, and MGMT were frequently methylated in benign samples as well as in malignant tumors, independent of microsatellite instability. In contrast, normal mucosa samples taken from bowels without tumor were rarely methylated for the same genes. Hypermethylated CRABP1, MLH1, NR3C1, RUNX3, and SCGB3A1 were shown to be identifiers of carcinomas with microsatellite instability. In agreement with the CIMP concept, MSI and mutated BRAF were associated with samples harboring hypermethylation of several target genes. Conclusion Methylated ADAMTS1, MGMT, and MAL are suitable as markers for early tumor detection.

• Lind, Gruo Elisabeth; Skotheim, Rolf Inge & Lothe, Ragnhild A (2007). The epigenome of testicular germ cell tumors. APMIS - Journal of Pathologiy, Microbiology and Immunology. ISSN 0903-4641. 115, p. 1147–1160. Full text in Research Archive
• Wu, Q; Lothe, Ragnhild A; Ahlquist, Terje Cruickshank; Silins, I; Trope, CG & Micci, F [Show all 9 contributors for this article] (2007). DNA methylation profiling of ovarian carcinomas and their in vitro models identifies HOXA9, HOXB5, SCGB3A1, and CRABP1 as novel targets. Molecular Cancer. 6. doi: 10.1186/1476-4598-6-45. Full text in Research Archive Show summary

  Background The epigenetics of ovarian carcinogenesis remains poorly described. We have in the present study investigated the promoter methylation status of 13 genes in primary ovarian carcinomas (n = 52) and their in vitro models (n = 4; ES-2, OV-90, OVCAR-3, and SKOV-3) by methylation-specific polymerase chain reaction (MSP). Direct bisulphite sequencing analysis was used to confirm the methylation status of individual genes. The MSP results were compared with clinico- pathological features. Results Eight out of the 13 genes were hypermethylated among the ovarian carcinomas, and altogether 40 of 52 tumours were methylated in one or more genes. Promoter hypermethylation of HOXA9, RASSF1A, APC, CDH13, HOXB5, SCGB3A1 (HIN-1), CRABP1, and MLH1 was found in 51% (26/51), 49% (23/47), 24% (12/51), 20% (10/51), 12% (6/52), 10% (5/52), 4% (2/48), and 2% (1/51) of the carcinomas, respectively, whereas ADAMTS1, MGMT, NR3C1, p14 ARF, and p16 INK4awere unmethylated in all samples. The methylation frequencies of HOXA9 and SCGB3A1 were higher among relatively early-stage carcinomas (FIGO I-II) than among carcinomas of later stages (FIGO III-IV; P = 0.002, P = 0.020, respectively). The majority of the early-stage carcinomas were of the endometrioid histotype. Additionally, HOXA9 hypermethylation was more common in tumours from patients older than 60 years of age (15/21) than among those of younger age (11/30; P = 0.023). Finally, there was a significant difference in HOXA9 methylation frequency among the histological types (P = 0.007). Conclusion DNA hypermethylation of tumour suppressor genes seems to play an important role in ovarian carcinogenesis and HOXA9, HOXB5, SCGB3A1, and CRABP1 are identified as novel hypermethylated target genes in this tumour type.

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• Brodal, Hans Petter; Pharo, Heidi; Vedeld, Hege Marie & Lind, Guro Elisabeth (2025). PoDCall: a robust tool for automated droplet classification in DNA‐methylation droplet digital PCR. Molecular Oncology. ISSN 1574-7891. 19(9), p. 2472–2473. doi: 10.1002/1878-0261.70105. Full text in Research Archive
• Pharo, Heidi; Vedeld, Hege Marie; Wahlqvist, Rolf & Lind, Guro Elisabeth (2025). Re: Thomas Dreyer, Simone Brandt, Knud Fabrin, et al. Use of the Xpert Bladder Cancer Monitor Urinary Biomarker Test for Guiding Cystoscopy in High-grade Non-muscle-invasive Bladder Cancer: Results from the Randomized Controlled DaBlaCa-15 Trial. Eur Urol 2025;88:23–30. European Urology. ISSN 0302-2838. 88(6), p. e121–e121. doi: 10.1016/j.eururo.2025.07.028. Full text in Research Archive
• Lind, Guro Elisabeth & Korsvoll, Nils Hallvard (2023). Postdoktorene fortjener bedre betingelser. Full text in Research Archive
• Andreasen, Johan Kristian; Andreassen, Unni Soltun; Fossland, Trine; Høgestøl, Sofie Alexandra Engli; Lund, Ingrid & Lind, Guro Elisabeth [Show all 9 contributors for this article] (2023). Mangelfulle systemer for konfliktutsatte stipendiater. Full text in Research Archive
• Lind, Guro Elisabeth & Falkum, Ingrid Lossius (2021). En ny modell for postdoktorstillingen. Full text in Research Archive
• Søreide, Øystein; Olsen, Dag Rune; Lind, Guro Elisabeth & Holden, Lars (2020). Ingen forskning, ingen omstilling. Dagens næringsliv. ISSN 0803-9372. Full text in Research Archive
• Busterud, Guro & Lind, Guro Elisabeth (2018). Sløser med kvinnelig talent. p. 4–4. Full text in Research Archive
• Lind, Guro Elisabeth & Engeland, Manon van (2017). Details matter: the role of genomic location and assay standardization in DNA methylation analyses. Epigenomics. ISSN 1750-1911. 9(7), p. 933–935. doi: 10.2217/epi-2017-0053. Full text in Research Archive
• Aronsen, Jan Magnus; Jensenius, Alexander Refsum; Emblem, Kyrre Eeg; Storeng, Katerini Tagmatarchi; Enberg, Katja & Knutsen, Carl Henrik [Show all 7 contributors for this article] (2017). Kvalitetsparadokset i den norske forskningspolitikken. Full text in Research Archive Show summary

  De fleste insentivene norske forskere opplever i sin hverdag, er preget av kortsiktige resultater og målstyring mot kvantitet heller enn kvalitet. Dette er et kvalitetsparadoks i norsk forskningspolitikk. skriver flere medlemmer i Akademiet for yngre forskere.

• Storeng, Katerini Tagmatarchi; Midtbøen, Arnfinn Haagensen; Knutsen, Carl Henrik; DeMoor, Katrien & Lind, Guro Elisabeth (2017). Kampen om talentene. Full text in Research Archive
• Aronsen, Jan Magnus; Lind, Guro Elisabeth; Helland, Ingeborg Palm; Schomacker, Anders & Enberg, Katja (2017). Gode nyheter om unge forskeres karriereveier. Full text in Research Archive
• Aronsen, Jan Magnus; Lind, Guro Elisabeth; Helland, Ingeborg Palm; Schomacker, Anders; Enberg, Katja & Hølleland, Herdis (2017). Karriereveier for økt forskningskvalitet. Full text in Research Archive
• Høgestøl, Sofie A.E.; Lind, Guro Elisabeth; Moor, Katrien De; Storeng, Katerini Tagmatarchi; Knutsen, Carl Henrik & Midtbøen, Arnfinn Haagensen [Show all 7 contributors for this article] (2016). Karrièreusikkerhet tærer på unge forskere. p. 16–17. Full text in Research Archive
• Jeanmougin, M; Håvik, Annette Bentsen; Cekaite, Lina; Brandal, Petter; Sveen, Anders & Meling, Torstein Ragnar [Show all 11 contributors for this article] (2016). Primary and secondary glioblastomas: global expression analysis of two histologically indistinguishable tumor subtypes. Full text in Research Archive
• Lind, Guro Elisabeth; Schomacker, Anders & Hølleland, Herdis (2016). Karriereveier for framtidas postdoktorer. p. 32–33. Full text in Research Archive
• Schomacker, Anders; Lind, Guro Elisabeth & Hølleland, Herdis (2016). Etter festen kommer hverdagen. Full text in Research Archive
• Håvik, Annette Bentsen; Lind, Guro Elisabeth; Honne, Hilde; Meling, Torstein; Scheie, David & Hall, Kirsten Sundby [Show all 12 contributors for this article] (2014). Sequencing IDH1/2 glioma mutation hotspots in gliomas and malignant peripheral nerve sheath tumors. Neuro-Oncology. ISSN 1522-8517. 16(2), p. 320–322. doi: 10.1093/neuonc/not230. Full text in Research Archive
• Brackmann, Stephan; Pretorius, Maria E.; Klepp, Pasquale Catherine; Clausen, Ole Petter Fraas; Andersen, Solveig Norheim & Vatn, Morten H [Show all 9 contributors for this article] (2013). The distribution of chromosomal and microsatellite instability in colorectal cancers related to inflammatory bowel disease. Journal of Clinical Oncology. ISSN 0732-183X. 31(15). Full text in Research Archive
• Lind, Guro Elisabeth; Ahmed, Deeqa & Lothe, Ragnhild A (2012). Vimentin in Upper Gastrointestinal Pathologies-Letter. Cancer Epidemiology, Biomarkers and Prevention. ISSN 1055-9965. 21(10), p. 1889–1889. doi: 10.1158/1055-9965.EPI-12-0894. Full text in Research Archive
• Ahmed, Deeqa; Ågesen, Trude Holmeide; Danielsen, Stine Aske; Bretthauer, Michael; Thiis-Evensen, Espen & Hoff, Geir [Show all 10 contributors for this article] (2012). METHYLATION BASED BIOMARKERS FOR NON-INVASIVE EARLY DETECTION OF COLORECTAL CANCER. Annals of Oncology. ISSN 0923-7534. 23, p. 23–23. Full text in Research Archive
• Løvf, Marthe; Thomassen, Gard O Sundby; Lind, Guro Elisabeth; Lothe, Ragnhild A & Skotheim, Rolf Inge (2010). An oligo microarray design for detection of known and putative oncogenic fusion transcripts. European Journal of Cancer. ISSN 0959-8049. 8(5), p. 199–199. Full text in Research Archive
• Leithe, Edward; Sirnes, Solveig; Bruun, Jarle; Kjenseth, Ane Hansen; Lind, Guro Elisabeth & Kolberg, Matthias [Show all 10 contributors for this article] (2010). Post-translational mechanisms involved in downregulation of the gap junction protein Connexin43 in colorectal cancer. European Journal of Cancer. ISSN 0959-8049. 8(5), p. 138–138. Full text in Research Archive
• Danielsen, Stine Aske; Lind, Guro Elisabeth; Hall, Kirsten Sundby; Smeland, Sigbjørn; Berg, E van den & Mertens, F. [Show all 8 contributors for this article] (2010). Epigenetic target genes in malignant peripheral nerve sheath tumours identified as surrogate prognostic biomarkers. European Journal of Cancer. ISSN 0959-8049. 8(5), p. 43–43. Full text in Research Archive
• Lind, Guro Elisabeth; Danielsen, Stine Aske; Ahlquist, Terje Cruickshank; Merok, Marianne Aarstad; Rognum, Torleiv Ole & Meling, Gunn Iren [Show all 10 contributors for this article] (2009). A novel epigenetic biomarker panel for early detection of colorectal cancer and adenomas. European Journal of Cancer. ISSN 0959-8049. 7(2), p. 145–145. Full text in Research Archive
• Skotheim, Rolf Inge; Eken, Marthe; Thomassen, Gard O Sundby; Lind, Guro Elisabeth & Lothe, Ragnhild A (2009). A universal assay for detection of oncogenic fusion transcripts by oligo microarray analysis. European Journal of Cancer. ISSN 0959-8049. 7(2), p. 147–148. Full text in Research Archive
• Ahlquist, Terje Cruickshank; Thiis-Evensen, Espen; Lind, Guro Elisabeth; Meling, Gunn Iren; Vatn, Morten H & Hoff, Geir [Show all 8 contributors for this article] (2008). Potential cancer prevention markers can be identified by comparing gene methylation pattern in normal colon mucosa to those of benign and malignant tumours. Gastroenterology. ISSN 0016-5085. 134(4), p. A445–A445. Full text in Research Archive
• Lind, Gruo Elisabeth; Ahlquist, Terje Cruickshank & Lothe, Ragnhild A (2007). DNA hypermethylation of MAL: A promising diagnostic biomarker for colorectal tumors. Gastroenterology. ISSN 0016-5085. 132. doi: 10.1053/j.gastro.2007.03.003. Full text in Research Archive

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