Abstract 4243: Genetic variants frequently detected in Egyptian breast cancer tumors: Comprehensive cancer panel by ion torrent DNA sequencing technology

Abstract Breast cancer is the leading cause of cancer-related death in women worldwide. In Egypt, it is the most common cancer among females and its incidence is progressively increasing with a great tendency to occur with advanced stages in younger ages. Due to the heterogeneity of breast cancer, it was classified into different subtypes, each exhibits a unique gene mutation profile, based on biological characteristics and on gene expression pattern. Therefore, further research is needed to investigate the unknown genetic mutations involved in the progression of that disease. This study aimed to sequence 409 exons of tumor suppressor genes and oncogenes to identify the frequency of the detected genetic mutations in breast cancer using Ion Comprehensive Cancer Panel. Forty-eight tissue samples of various breast cancer subtypes were collected from National Cancer Institute (NCI) outpatient clinic, Cairo University. Analysis revealed 191 exonic and splicing variants. In this paper, we will address the most frequently detected Egyptian genetic variants (in 31.25 % of cases or more) as well as other deleterious variants commonly associated with breast cancer. Most of the detected genetic variants were checked in 1000g, dbSNP and Exac All databases. Other variants were found at known hotspot sites. We reported fifty-one somatic and germline mutations in thirty-two genes; AKAP9, BUB1B, RPS6KA2, AURKB, FANCA, RNF213, FGFR4, KAT6B, NLRP1, KAT6A, PER1, ERBB4, IL6ST, PIK3CA, P53, AURKA, WRN, PALB2, PTEN, GATA3, AKT1, ERBB2 and KRAS. Only KAT6B incurred non-frameshift deletion and only GATA3 had frameshift insertion while KAT6A, ERBB4 and PTEN had frameshift deletion. All the identified variants were detected with different frequencies in each breast cancer subtype. Each sample harbored at least four mutations and the maximum number of mutations per sample was twelve. The current data showed that gene panels analyzed by Next-Generation Sequencing (NGS) identifies large number of germline and somatic mutations that is crucial for understanding cancer predisposition and developing personalized or combination therapies that efficiently target the individual breast cancer-specific mutations. Key words: Breast cancer, Somatic mutations, Germline mutations, Ion torrent sequencing, Targeted sequencing. Note: This abstract was not presented at the meeting. Citation Format: Abdel-Rahman N. Zekri, Osman Mansour, Samah A. Loutfy, Mohamed M. Hafez, M. Gomaa, Abeer Bahnassy, Mai M. Lotfy, Amira S. Youssef, Ola S. Ahmed, Mohammed Abouelhouda, Auhood Nassar. Genetic variants frequently detected in Egyptian breast cancer tumors: Comprehensive cancer panel by ion torrent DNA sequencing technology [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 4243.