High frequency of pathogenic germline variants in genes associated with homologous recombination repair in patients with advanced solid cancers

We identified pathogenic and likely pathogenic variants in 17.8% of the patients within a wide range of cancer types. In particular, mesothelioma, ovarian cancer, cervical cancer, urothelial cancer, and cancer of unknown primary origin displayed high frequencies of pathogenic variants. In total, 22 BRCA1 and BRCA2 germline variant were identified in 12 different cancer types, of which 10 (45%) variants were not previously identified in these patients. Pathogenic germline variants were predominantly found in DNA repair pathways; approximately half of the variants were within genes involved in homologous recombination repair. Loss of heterozygosity and somatic second hits were identified in several of these genes, supporting possible causality for cancer development. A potential treatment target based on pathogenic germline variant could be suggested in 25 patients (4%). investigation of expression features related to Class 4 and 5 germline mutations in cancer patients