Abstract 2751: Identification of predisposition genes involved in thyroid and breast carcinomas in patients with family history of these tumors by whole exome sequencing

Abstract

Abstract A significant number of patients with family history of breast (BC) and papillary thyroid carcinomas (PTC) have been detected at Oncogenetics Dept of AC Camargo Cancer Center, SP, Brazil. The aim of this study was to identify genetic alterations in patients with family cancer history of BC and TC by using whole exome sequencing (WES) analysis. All patients included in this study fulfilled the inclusion criteria as follows: proband with non-medullary TC and/or BC with family cancer history of these tumors AND at least two 1st- or 2nd- degree relatives with one of these tumors either diagnosed <45 years old OR one 1st- relative with one of these tumors and proband diagnosed <40 years old AND history of other tumors. Exclusion criteria comprised female patients with BC treated by radiotherapy before TC diagnosis and probands affected with common mutations in major hereditary predisposition genes. Twenty-four blood samples and four tumor samples were included in WES analysis. Libraries were prepared by using Nextera Exome Enrichment kit following manufacturer's instructions and were sequenced in HiSeq2000 sequencer (Illumina). An average depth of 95x was obtained. The analysis focusing in single nucleotide polymophisms (SNPs) in high penetrance genes detected 12 SNPs in six genes. Particularly, two potential pathogenic SNPs mapped at BRCA1 gene, previously associated with PTC and BC, were detected in at least 25% of samples. The evaluation of rare pathogenic alterations shared by all cases revealed two single nucleotide variations (SNVs) mapped at HYDIN gene. Alternative variants of HYDIN gene were previously detected in serum of patients diagnosed with colorectal, lung, breast and thyroid tumors [Laske K et al, Cancer Immunol Res 1: 190, 2013]. Further analyses are needed to confirm these alterations as potential predisposition candidates associated with breast and thyroid hereditary carcinomas. Furthermore, the data generated in this study could be incorporated into the general knowledge of cancer genetics, allowing the development of prevention strategies, screening and genetic counseling in these families. Financial Support: FAPESP (2013/01867-8 and 2014/03983-8) and CNPq (481132/2012-0) Citation Format: Maisa Pinheiro, Fabio Marchi, Sandra Drigo, Patricia Reis, Luiz Lehmann Coutinho, Sonia Andrade, Luis Paulo Kowaslki, Maria Isabel Achatz, Silvia Rogatto. Identification of predisposition genes involved in thyroid and breast carcinomas in patients with family history of these tumors by whole exome sequencing. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 2751. doi:10.1158/1538-7445.AM2015-2751