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

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. and were the most top two frequently mutated genes. We detected 15 different somatic mutations in and 8 different ones in , each in 27 samples (58.7%). According to Clinvar database; we found 19 pathogenic somatic mutations: 7 in , 5 in , and single variants of , , , , and We also identified 5 variants with uncertain significance (4 in and 1 in ) and 4 variants with conflicting interpretations of pathogenicity (2 in and 1 in each of and ). Moreover, one drug response variant (p.P72R) in was detected in 8 samples. Furthermore, four novel variants were identified in , , and . 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.