BRCA1 and BRCA2 rearrangements in Brazilian individuals with Hereditary Breast and Ovarian Cancer Syndrome

• Type: Article in International Scientific Journal
• Date: 2016

Authors

Ewald, IP (Author) Other; Cossio, SL (Author) Other; Palmero, EI (Author) Other; Pinheiro, M (Author) Other; de Oliveira Nascimento, ILD (Author) Other; Bonfim Machado, TMB (Author) Other; Sandes, KA (Author) Other; Toralles, B (Author) Other; Garicochea, B (Author) Other; Izetti, P (Author) Other; Saraiva Pereira, MLS (Author) Other; Bock, H (Author) Other; Vargas, FR (Author) Other; Martins Moreira, MAM (Author) Other; Peixoto, A (Author) Other; Manuel R Teixeira (Author) ICBAS; Ashton Prolla, P (Author) Other

Journal

Title: Genetics and Molecular Biology

Vol. 39

Pages: 223-231

ISSN: 1415-4757

Publisher: Sociedade Brasileira de Genetica

Indexing

ISI Web of Knowledge - 17 Citations

Scopus - 17 Citations

Other information

Authenticus ID: P-00K-JSR

DOI: 10.1590/1678-4685-gmb-2014-0350

Abstract (EN): Approximately 5-10% of breast cancers are caused by germline mutations in high penetrance predisposition genes. Among these, BRCA1 and BRCA2, which are associated with the Hereditary Breast and Ovarian Cancer (HBOC) syndrome, are the most frequently affected genes. Recent studies confirm that gene rearrangements, especially in BRCA1, are responsible for a significant proportion of mutations in certain populations. In this study we determined the prevalence of BRCA rearrangements in 145 unrelated Brazilian individuals at risk for HBOC syndrome who had not been previously tested for BRCA mutations. Using Multiplex Ligation-dependent Probe Amplification (MLPA) and a specific PCR-based protocol to identify a Portuguese founder BRCA2 mutation, we identified two (1,4%) individuals with germline BRCA1 rearrangements (c.547+240_5193+178del and c.4675+467_5075-990del) and three probands with the c.156_157insAlu founder BRCA2 rearrangement. Furthermore, two families with false positive MLPA results were shown to carry a deleterious point mutation at the probe binding site. This study comprises the largest Brazilian series of HBOC families tested for BRCA1 and BRCA2 rearrangements to date and includes patients from three regions of the country. The overall observed rearrangement frequency of 3.44% indicates that rearrangements are relatively uncommon in the admixed population of Brazil.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 9