P7: Clinical validation of a next-generation sequencing for germline mutations in BRCA1 and BRCA2 genes in breast cancer.

Breast cancer is the most common cancer affecting women all over the world. The World Health Organization estimated that 1.38 million breast cancers were diagnosed worldwide in 2008. In Morocco, according to the Greater Casablanca Cancer Registry, breast cancer seems to be the first female cancer with a standardized incidence of 36.4 for an average age of 49.5 years. Germline mutations that inactivate BRCA1 and BRCA2 are responsible for breast and ovarian cancer susceptibility. The prevalence of BRCA1 and BRCA2 mutations where family history shows more than one occurrence of breast cancer under the age of 50 ranges from 8 to 21.2%. High throughput methods such as next generation sequencing are increasingly used in molecular diagnosis. Massive parallel sequencing allows the generation of millions of DNA sequences in a single run with low cost per base. Recently, next generation sequencing methods for the mutation analysis of the BRCA1 and BRCA2 genes in patients with breast and ovarian cancer have been described using both high capacity and bench top platforms. We utilized a workflow using the Ion Torrent Personal Genome Machine (IT-PGM; Life Technologies) an NGS platform, to screen germline mutations in BRCA1 and BRCA2 genes using the Ion AmpliSeq BRCA1 and BRCA2 Community Panel (Life Technologies). Till now, 16 breast cancer patients, considered being at high risk, due to medicinal examination were selected for molecular genetic testing of BRCA1 and BRCA2 genes. Mutations detected by IT-PGM platform were confirmed by traditional mutation detection assay Sanger sequencing. We show that the IT-PGM platform is sensitive and specific and can be used for routine mutational screening of patient with hereditary breast and ovarian cancers. [ABSTRACT FROM AUTHOR]