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

Autor(es)

Ferreira, Elisa Napolitano ^[1] ; Brianese, Rafael Canfield ^[1] ; Bueno de Almeida, Renan Valieris ^[1] ; Drummond, Rodrigo Duarte ^[1] ; de Souza, Jorge Estefano ^{[2, 3]} ; da Silva, Israel Tojal ^[1] ; de Souza, Sandro Jose ^{[4, 3]} ; Carraro, Dirce Maria ^{[1, 5]}

Afiliação do(s) autor(es)

^[1] AC Camargo Canc Ctr, Int Res Ctr, CIPE, Sao Paulo, SP - Brazil

^[2] Univ Fed Rio Grande do Norte, Inst Metropole Digital, Natal, RN - Brazil

^[3] Univ Fed Rio Grande do Norte, Bioinformat Multidisciplinary Environm BioME, Natal, RN - Brazil

^[4] Univ Fed Rio Grande do Norte, Brain Inst, Natal, RN - Brazil

^[5] Natl Inst Sci & Technol Oncogen & Therapeut Innov, Sao Paulo, SP - Brazil

• Tipo de documento: Artigo Científico
• Fonte: TRANSLATIONAL ONCOLOGY; v. 12, n. 11, p. 1453-1460, NOV 2019.
• Citações Web of Science: 0

Resumo

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 data presented here indicate that in the absence of BRCA1 germline mutations, a higher number of driver mutations are required for tumor development and that different defective processes are operating in the tumorigenesis of hereditary and sporadic TNBC in young women. (AU)

• Processo FAPESP: 13/23277-8 - Aspectos moleculares envolvidos no risco, desenvolvimento e progressão do carcinoma ductal de mama: busca de novos genes de susceptibilidade e investigação da progressão do carcinoma in situ e do papel da mutação em BRCA1 no tumor triplo negativo
• Beneficiário: Dirce Maria Carraro
• Modalidade de apoio: Auxílio à Pesquisa - Temático