Journal of Advanced Research

Journal of Advanced Research

Volume 24, July 2020, Pages 149-157
Journal of Advanced Research

Targeted next generation sequencing identifies somatic mutations in a cohort of Egyptian breast cancer patients

https://doi.org/10.1016/j.jare.2020.04.001Get rights and content
Under a Creative Commons license
open access

Highlights

  • Identifying somatic mutations associated with Egyptian breast cancer tumors.

  • Identifying breast cancer mutation driver genes in the studied Egyptian patients.

  • Identify genetic mutations in BC tumors help developing personalized treatment protocols or combination therapies.

  • Identifying novel variants that may be associated with Egyptian breast cancer patients.

  • Help in customization of Egyptian related breast cancer panels as a routine work

Abstract

Breast cancer (BC) incidence is progressively increasing in Egypt. However, there is insufficient knowledge of the acquired somatic mutations in Egyptian BC patients which limit our understanding of its progression. To the best of our knowledge, this is the first Egyptian cohort to sequence a multiple-gene panel of cancer related genes on BC patients. Four hundred and nine cancer related genes were sequenced in 46 fresh breast tumors of Egyptian BC patients to identify somatic mutations and their frequencies.

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%). According to Clinvar database; we found 19 pathogenic somatic mutations: 7 in Tp53, 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, one drug response variant (p.P72R) in TP53 was detected in 8 samples. Furthermore, four novel variants were identified in JAK2, MTOR, KIT and EPHB. Further analysis, by Ingenuity Variant Analysis software (IVA), showed that PI3K/AKT signaling is altered in greater than 50% of Egyptian BC patients which implicates PI3K/AKT signaling as a therapeutic target. In this cohort, we shed the light on the most frequently detected somatic mutations and the most altered pathway in Egyptian BC patients.

Keywords

Breast cancer
Somatic mutations
Target sequencing
Ion torrent sequencing
Next Generation Sequencing

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Peer review under responsibility of Cairo University.