Abstract 1245: Identification of germline variants in cancer susceptibility genes in patients with hereditary breast and ovarian cancer syndrome by massive parallel sequencing in Argentinean population

Abstract

Breast cancer is the most frequent cancer and ovarian cancer the seventh most frequent cancer among females worldwide, representing approximately 25% and 4% of all cancers. In Argentina, breast cancer and Ovarian cancer cause 6163 and 1332 deaths per year, respectively. Both breast and ovarian cancers are heterogeneous diseases composed of different tumor types with distinctive features and behaviors. The main risk factors for breast and ovarian cancer include age, family history, and genetics.The genetic components of both of the diseases have been well established, contributing to up to 10% of all breast cancer cases and 15% of all ovarian cancer cases.The two major susceptibility genes for both diseases are BRCA1 and BRCA2, and several other susceptibility genes have been identified. However, in the majority of high-risk breast and/or ovarian cancer (HBOC) families, the genetic predisposition factors remain unidentified, making the genetic counseling of these families challenging. The aim of the current study is to utilize an NGS approach to identify genetic factors that predispose individuals to hereditary breast and/or ovarian cancer (HBOC) in the high-risk Argentinian BRCA1/2 mutation-negative HBOC patients.16 patients were analyzed, the DNA was extracted from a blood samples and was subjected to a targeted massively parallel sequencing platform comprising 141 cancer predisposition genes. We detected in these patient 6 pathogenic variants in SBDS, FANCA, MC1R, WRN, MSR1 and SDHD genes. The effect of these variants are of type: non-synonymous (67%) and stop codon gains (33%). We also found 6 variants of uncertain significance (VUS) in APC, RAD50, SDHB, FANCD2, MLH1 and CDH1 genes.In conclusion, the identification of new variants could help to discover new genes associated to HBOC in the population of Argentina.These findings provide an excellent premise for further studies and could be utilized in the design of more efficient clinical management strategies for HBOC. Citation Format: Alejandra Franco, Fernando Orti, Sandra Perdomo, Cecilia Riggi, Cecilia Frecha, Javier Oliver. Identification of germline variants in cancer susceptibility genes in patients with hereditary breast and ovarian cancer syndrome by massive parallel sequencing in Argentinean population [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 1245.