Reporting the clinical impact of germline variants in human cancers

“Many human cancers are rooted in rare germline mutations, but identifying them and understanding their clinical impact is a considerable challenge. We have created a comprehensive bioinformatics workflow that successfully prioritizes cancer-predisposing DNA variants detected from high-throughput sequencing. Importantly, our reporting tool also highlights any variant with implications for prognosis or treatment options”, says Eivind Hovig, Professor and leader of the Centre for Bioinformatics.

The study, financed by the Norwegian Research Council, was recently published in the International Journal of Cancer and can be found here. The bioinformatics tool is named Cancer Predisposition Sequencing Reporter (CPSR), and was established in collaboration with researchers at Oslo University Hospital and researchers from the University of Melbourne in Australia.

Screening of cancer patients for predisposing germline alterations may yield valuable decision support for risk-reducing interventions and surveillance. The presence of specific pathogenic germline variants (e.g. in BRCA1/2) can also have strong implications when it comes to drug response. However, the growing amount of knowledge regarding cancer-predisposing genes and their potential impact on prognosis and treatment is dispersed across multiple databases and online resources. Interpretation of raw variant sets from genetic testing of cancer patients can thus be a significant challenge. The Cancer Predisposition Sequencing Reporter (CPSR) was developed to meet this need. CPSR integrates data from a number of gene and variant databases, and produces interactive and clinically oriented sequencing reports for each cancer case. The tool is open-source and publicly available through its GitHub page.

“The implementation of cancer precision medicine requires a careful understanding of both acquired tumor variants and inherited variants in each cancer patient. CPSR constitutes in this regard a highly valuable complement to our other decision-support tool for somatic aberrations, the Personal Cancer Genome Reporter (PCGR)”, says Sigve Nakken, researcher at Oslo University Hospital, and lead author of the paper.

Published Aug. 10, 2021 11:41 AM - Last modified Aug. 10, 2021 11:41 AM