Humaid O Al-Shamsi
The University of Texas, USA
Title: Molecular spectra, frequencies, and distribution patterns of somatic mutations using next generation sequencing in Arab women with breast cancer
Biography
Biography: Humaid O Al-Shamsi
Abstract
Purpose: Breast cancer in Arab world has unique clinicopatholigical features including early onset, higher grade and higher HER2 amplification, the aim of this retrospective study was to assess the molecular spectra, frequencies, and distribution patterns of somatic mutations using next generation sequencing (NGS) in Arab women with breast cancer.
Subjects & Methods: 78 consecutive Arab women with breast cancer whose tumors had been evaluated using NGS were identified and retrospectively reviewed. We recorded patient characteristics, tumor pathological features, the rate of somatic mutations found on the NGS.
Results: The median age at diagnosis was 52.3 years (range: 37-82 years). 30 (38.5%) of the 78 patients were 50 years of age or younger. A familial history of breast cancer was documented in 30 (38.5%) patients. NGS revealed the following somatic mutation rates: TP53, 23%; ATM, 2.5%; IDH1, 2.5%; IDH2, 3.8%; PTEN, 7.7%; PIK3CA, 15.4%; APC, 7.7%; NPMA1, 1.3%; MPL, 1.3%; JAK2, 2.5%; KIT, 7.7%; KRAS, 3.8%; NRAS, 3.8%. DH1 and IDH2 were 2.5% and 3.8% respectively. Two patients (2.5%) had JAK2 mutations and both had an advanced triple-negative disease. Compared with Western population, Arab women have higher rates of APC, PTEN, KIT, KRAS, NRAS and DH1 somatic mutations and lower rates of TP53 and PIK3CA somatic mutations compared to Western women. ATM mutation rate was similar. Two novel somatic mutations were identified NPM1 and MPL with undefined role in breast cancer pathogenesis.
Conclusions: Our results revealed differences in the genetic profiles and mutation hotspots in Arab women with breast cancer compared to the reported genetic profiles of Western women with breast cancer. These results may have clinical implications in some of the actionable mutations and their targeted therapies once the roles of these somatic mutations in breast cancer tumorigenesis are more defined.