An integrated somatic and germline approach to aid interpretation of germline variants of uncertain significance in cancer susceptibility genes.

ABSTRACT: Genomic profiles of tumors are often unique and represent characteristic mutational signatures defined by DNA damage or DNA repair response processes. The tumor-derived somatic information has been widely used in therapeutic applications, but it is grossly underutilized in the assessment of germline genetic variants. Here, we present a comprehensive approach for evaluating the pathogenicity of germline variants in cancer using an integrated interpretation of somatic and germline genomic data. We have previously demonstrated the utility of this integrated approach in the reassessment of pathogenic germline variants in selected cancer patients with unexpected or non-syndromic phenotypes. The application of this approach is presented in the assessment of rare variants of uncertain significanc

SUBMITTER: Schwartz A 

PROVIDER: S-EPMC9453486 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature