Analysis of brca1 and brca2 in women affected or with positive family history of breast and ovarian cancers

Breast cancer is the most common malignancy diagnosed among women and second leading cause of cancer-related death in them. 5–10% of breast cancer cases are hereditary and several loci have been identified to paly role in these cases. Next-generation sequencing (NGS), a high throughout method, can analyze multiple genes for detecting individuals at risk for developing breast/ovarian cancer. Here, we aim to report the finding of analysis of BRCA1 and BRCA2 in more than 200 woman with Breast or Ovarian cancers or a positive family history of these cancers. Targeted NGS was applied to analyze 229 samples from woman with clinical presentation of breast/ovarian cancer (n=135) or asymptomatic females with positive family history of the disease (n=94). Target regions capture with Nimblegen chip was performed and followed by Next Generation Sequencing on Illumina platform. In 50 samples out of 229 analyzed samples (~ 22%), at least one variant with VUS (Variant with Uncertain Significance), likely pathogenic, or pathogenic classification were found based on ACMG guidelines for variant interpretation. Among these, the most common variant type was missense. All different type of single nucleotide changes, and also copy number variations were detected in the analyzed samples. Among the variants, a large number of novel variants were detected, showing the different genetic epidemiology of BRCA1 and 2 variants in Iranian population in comparison to other nations. The spectrum of detected variations and their frequencies will be presented in the meeting. This study showed that first of all,NGS is a powerful technology in detecting all different intragenic variations in BRCA1 and 2 genes, including single nucleotide changes as well as intragenic copy number variations. Secondly, thespectrum of variants detected in this study, is a very good representative of genetic epidemiology of BRCA1 and BRCA2 variants in Iranian population that can also show the differences with other populations

Keywords:

Breast Cancer , Ovarian Cancer , Gene and Cancer , Lifestyle and Cancer , Cancer Genetics