Molecular pathology selected abstracts
December 2020—Next-generation sequencing-based mutation testing of various cancer types is clinically indicated and widely used to diagnose disease, inform potential therapeutic targets, prognosticate disease course, and monitor responses to targeted and nontargeted therapies. The genetic variants discovered by tumor-based next-generation sequencing (NGS) can be somatically acquired by the neoplastic cells or a fixed inherited component of the patient’s germline genome. Distinguishing the germline versus somatic status of tumor NGS-defined variants is of significant clinical importance not only for patient care but possibly for patients’ families. Because many cancers have a substantial inherited component, the discovery of a pathogenic germline mutation by tumor-based NGS may have substantial familial implications. For example, being aware of a cancer risk allele, such as BRCA1, can lead to the use of highly effective interventions to prevent or treat the related cancer in family members. Consensus guidelines recommend germline genetic testing only for those cancer patients who have a clinical presentation or family history suggestive of hereditary disease.