Identification and characterization of germline pathogenic variants using matched tumor-normal next-generation sequencing in 7363 pan-cancer patients in China.

1545Background: Comprehensive NGS panel based genetic testing is becoming more common to help clinicians provide personalized cancer care. Matched tumor-normal sequencing is recommended primarily to detect tumor-specific variants. Previously under-explored, it could also detect pathogenic germline alterations in cancer patients. Using targeted matched tumor-normal NGS, we identified and characterized germline variants in a large pan-cancer patient cohort in China. Methods: We surveyed the germline variants in 7363 Chinese patients across more than 18 diverse cancer types. Germline variants in 62 cancer-susceptibility genes were called from a 1021 gene NGS panel analyzing matched normal DNA. Following AMCG guidelines, variants were classified into pathogenic, likely pathogenic, variant of unknown significance, likely benign, or benign. Results: 385 germline pathogenic and likely pathogenic variants (GPVs) were identified in 374/7363 (5.1%) patients. Ovarian cancer (27.6%, 37/134) represented the highest pr...