BRCA1 and BRCA2 rearrahgements in brazilian individuals with hereditary breast and ovarian cancer syndrome

• Autor(a) principal: Ewald, Ingrid Petroni
• Data de Publicação: 2016
• Outros Autores: Cossio, Silvia Liliana, Palmero, Edenir Inêz, Pinheiro, Manuela, Nascimento, Ivana Lucia de Oliveira, Machado, Taisa Manuela Bonfim, Sandes, Kiyoko Abé, Toralles, Betânia, Garicochea, Bernardo, Ribeiro, Patrícia Lisbôa Izetti, Pereira, Maria Luiza Saraiva, Bock, Hugo, Vargas, Fernando Regla, Moreira, Miguel Angelo Martins, Peixoto, Ana, Teixeira, Manuel R., Prolla, Patrícia Ashton
• Tipo de documento: Artigo
• Idioma: eng
• Título da fonte: Repositório Institucional da UFRGS
• Texto Completo: http://hdl.handle.net/10183/147444
• topic: Neoplasias da mama; Neoplasias ovarianas; Breast cancer; Hereditary breast and ovarian cancer syndrome; Gene rearrangements; BRCA gene.

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 forBRCA 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.