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Abstract
Breast cancer (BC) is the leading cause of cancer-related death in women worldwide and its incidence is progressively increasing in Egypt. Recent advances in next generation sequencing have been used to detect the acquired somatic mutations driving BC. However, there is insufficient knowledge of the acquired somatic mutations in Egyptian BC patients which limit our understanding of disease progression. Up to our knowledge, this is the first Egyptian cohort to sequence a multiple-gene panel of cancer related genes on BC patients.
409 cancer related genes were sequenced in 46 fresh breast tumors of Egyptian BC patients to identify somatic mutations and their frequencies, using the Ion Ampliseq Comprehensive Cancer Panel based on the Ion torrent DNA sequencing technology. The identified sequences were mapped to the human reference genome (hg19) and the detected genetic variants were annotated against different reference databases. The average depth of coverage is 668X and the average of the aligned reads which cover the target regions is 99.6%.
Our results showed that TP53 and PIK3CA were the most top two frequently mutated genes. We detected 15 different somatic mutations in TP53 and 8 different ones in PIK3CA, each in 27 samples (58.7%). Most of the detected somatic mutations in TP53 and PIK3CA are pathogenic and well established in known hotspot regions. According to Clinvar database; we found 19 pathogenic somatic mutations: 7 in p53, 5 in PIK3CA, and single variants of VHL, STK11, AKT1, KRAS, IDH2, PTEN and ERBB2. We also identified 5 variants with uncertain significance (4 in TP53 and 1 in CEBPA) and 4 variants with conflicting interpretations of pathogenicity (2 in TP53 and 1 in each of APC and JAK3). Moreover, 4 novel variants were identified in JAK2, MTOR, KIT and EPHB.
In this cohort, we shed the light on the most frequently detected somatic mutations in Egyptian BC patients which allows for more knowledge about BC progression.
Citation Format: Auhood Nassar, Mohamed abouelhoda, Abeer Bahnassy, Amira Salah El-Din Youssef, Mai M. Lotfy, ola S. Ahmed, Hoda Ismail, Abdel-Rahman N. Zekri. Targeted next generation sequencing identifies somatic variants in Egyptian breast cancer patients [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 2491.