Influence of BRCA1 Germline Mutations in the Somatic Mutational Burden of Triple-Negative Breast Cancer.

Influence of BRCA1 Germline Mutations in the Somatic Mutational Burden of Triple-Negative Breast Cancer. Transl Oncol. 2019 Aug 13;12(11):1453-1460 Authors: Ferreira EN, Brianese RC, de Almeida RVB, Drummond RD, de Souza JE, da Silva IT, de Souza SJ, Carraro DM Abstract The majority of the hereditary triple-negative breast cancers (TNBCs) are associated with BRCA1 germline mutations. Nevertheless, the understanding of the role of BRCA1 deficiency in the TNBC tumorigenesis is poor. In this sense, we performed whole-exome sequencing of triplet samples (leucocyte, tumor, and normal-adjacent breast tissue) for 10 cases of early-onset TNBC, including 5 hereditary (with BRCA1 germline pathogenic mutation) and 5 sporadic (with no BRCA1 or BRCA2 germline pathogenic mutations), for assessing the somatic mutation repertoire. Protein-affecting somatic mutations were identified for both mammary tissues, and Ingenuity Pathway Analysis was used to investigate gene interactions. BRCA1 and RAD51C somatic promoter methylation in tumor samples was also investigated by bisulfite sequencing. Sporadic tumors had higher proportion of driver mutations (≥25% allele frequency) than BRCA1 hereditary tumors, whereas no difference was detected in the normal breast samples. Distinct gene networks were obtained from the driver genes in each group. The Cancer Genome Atlas data analysis of TNBC classified as hereditary and sporadic reinforced our findings. The da...
Source: Translational Oncology - Category: Cancer & Oncology Authors: Tags: Transl Oncol Source Type: research