Tumor sequencing aids to identify individuals with hereditary cancer.

Abstract

e13678 Background: Early identification of individuals with hereditary cancer significantly improves survival in patients and relatives. New genomic tools can identify germline pathogenic variants via tumor-only genomic sequencing in addition to treatment guiding biomarkers. Methods: Our tumor sequencing protocol in medical practice since 2018 via Oncomine Comprehensive Assay (OCA) interrogates several hereditary cancer associated genes; therefore, we aimed to evaluate OCA’s capacity to point out individuals’ with hereditary cancer. But first, OCA’s technical validity was evaluated by testing up to 20 year old FFPE block isolated tumor genomes of individuals known to carry 19 pathogenic variants. Results: All variants were present in the OCA raw dataset but 26% were not called by the commercial software due to specificity of the variant calling algorithm and bias caused by amplicon-based enrichment and limited coverage. Even with this limitation, OCA’s clinical utility was evaluated next. A pathogenic variant candidate to be germline was identified in 5% (26/510) of tumor genomes routinely tested looking for treatment guiding biomarkers, but up to 8% (26/317) when excluding lung cancer patients. Importantly, 73% (14/19) of the ones that were followed-up by peripheral blood testing were confirmed to be germline, so inherited nature of the cancer was confirmed in 9% of ovarian, 8% of endometrium, 5% of biliary tract, 4% of breast, 1% of colorectal and 1% of lung cancer patients whose tumor genome was tested for routine treatment guiding biomarker identification. Conclusions: OCA is a useful genomic tool for identifying individuals with hereditary cancer that opens a new era in clinical practice in oncology. An increased awareness among physicians about this new genomic tool includes understanding the importance of peripheral blood confirmation to define the germline nature of the OCA-identified candidate variant; and proper genetic counseling and germline testing when OCA does not find a candidate variant in a patient with strong family history due to the lack of comprehensive identification of every type of pathogenic variants in all known genes associated with inherited cancer via tumor sequencing tools like OCA.