RESUMO
PURPOSE: There is still a considerable percentage of hereditary breast and ovarian cancer (HBOC) cases not explained by BRCA1 and BRCA2 genes. In this report, next-generation sequencing (NGS) techniques were applied to identify novel variants and/or genes involved in HBOC susceptibility. METHODS: Using whole exome sequencing, we identified a novel germline mutation in the moderate-risk gene ATM (c.5441delT; p.Leu1814Trpfs*14) in a family negative for mutations in BRCA1/2 (BRCAX). A case-control association study was performed to establish its prevalence in Spanish population, in a series of 1477 BRCAX families and 589 controls further screened, and NGS panels were used for ATM mutational screening in a cohort of 392 HBOC Spanish BRCAX families and 350 patients affected with diseases not related to breast cancer. RESULTS: Although the interrogated mutation was not prevalent in case-control association study, a comprehensive mutational analysis of the ATM gene revealed 1.78% prevalence of mutations in the ATM gene in HBOC and 1.94% in breast cancer-only BRCAX families in Spanish population, where data about ATM mutations were very limited. CONCLUSION: ATM mutation prevalence in Spanish population highlights the importance of considering ATM pathogenic variants linked to breast cancer susceptibility.
Assuntos
Proteínas Mutadas de Ataxia Telangiectasia/genética , Neoplasias da Mama/epidemiologia , Neoplasias da Mama/genética , Estudos de Associação Genética , Predisposição Genética para Doença , Mutação em Linhagem Germinativa , Adulto , Proteínas Mutadas de Ataxia Telangiectasia/metabolismo , Estudos de Casos e Controles , Análise Mutacional de DNA , Feminino , Genes BRCA1 , Genes BRCA2 , Humanos , Imuno-Histoquímica , Perda de Heterozigosidade , Linhagem , Prevalência , Espanha/epidemiologia , Sequenciamento do ExomaRESUMO
Colorectal cancer is the first cause of cancer in occidental countries if we consider both male and females tumours. In Spain, 26,000 new cases are diagnosed every year. The possibilities of cure are higher if the tumour is diagnosed early. One of the most important risk factors for colorectal cancer is inheritance. Some hereditary syndromes, such as familial adenomatous polyposis (FAP), increase the risk by almost 100% and at a young age. Other more prevalent syndromes, such Lynch syndrome, increase the risk 10-12 times more than in the general population. This article aims at summarising the most important aspects in hereditary colorectal cancer and to be a useful tool to oncologists who work with these patients and their families (AU)
