Influence of BRCA1 germline mutations in the somatic mutational burden of triple-negative breast cancer

Ferreira, Elisa Napolitano; Brianese, Rafael Canfield; Almeida, Renan Valieris Bueno de; Drummond, Rodrigo Duarte; Souza, Jorge Estefano de; Silva, Israel Tojal da; Souza, Sandro José de; Carraro, Dirce Maria

Influence of BRCA1 germline mutations in the somatic mutational burden of triple-negative breast cancer

Página do item simplificado Estatísticas

dc.contributor.author	Ferreira, Elisa Napolitano
dc.contributor.author	Brianese, Rafael Canfield
dc.contributor.author	Almeida, Renan Valieris Bueno de
dc.contributor.author	Drummond, Rodrigo Duarte
dc.contributor.author	Souza, Jorge Estefano de
dc.contributor.author	Silva, Israel Tojal da
dc.contributor.author	Souza, Sandro José de
dc.contributor.author	Carraro, Dirce Maria
dc.date.accessioned	2019-09-05T16:29:47Z
dc.date.available	2019-09-05T16:29:47Z
dc.date.issued	2019-08
dc.description.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.	pt_BR
dc.identifier.citation	FERREIRA, E. N.; BRIANESE, R. C.; ALMEIDA, R. V. B.; DRUMMOND, R. D.; SOUZA, J. E.; SILVA, I. T.; SOUZA, S. J.; CARRARO, D. M. Influence of BRCA1 germline mutations in the somatic mutational burden of triple-negative breast cancer. Transl Oncol., [s. l.], v. 12, n. 11, p. 1453-1460, ago. 2019. DOI: 10.1016/j.tranon.2019.07.016. Disponível em: https://www.sciencedirect.com/science/article/pii/S1936523319302232?via%3Dihub. Acesso em: 05 set. 2019.	pt_BR
dc.identifier.doi	10.1016/j.tranon.2019.07.016
dc.identifier.uri	https://repositorio.ufrn.br/jspui/handle/123456789/27644
dc.language	en	pt_BR
dc.subject	Breast neoplasms	pt_BR
dc.subject	triple negative breast neoplasms	pt_BR
dc.subject	BRCA1	pt_BR
dc.title	Influence of BRCA1 germline mutations in the somatic mutational burden of triple-negative breast cancer	pt_BR
dc.type	article	pt_BR