Helical and kinase domain mutations of , and their association with hormone receptor expression in breast cancer.

Breast cancer is one of the major causes of female morbidity and mortality, accounting for ~25% of the total cancer cases in women. Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic α subunit () mutations serve a major role in downstream signaling of receptor tyrosine kinases. The present study aimed to elucidate the frequency of exon 9 and 20 mutations of and their role in disease progression. A total of 118 tumor samples from confirmed breast cancer patients were collected from the histopathology laboratory at King Fahd Hospital of the University (Al-Khobar, Saudi Arabia). Sanger sequencing was performed on extracted DNA to identify the mutations on exons 9 and 20 of . The results were further validated by competitive allele-specific TaqMan polymerase chain reaction. Three mutations, namely E542K and E545K within exon 9, and H1047R within exon 20, were observed in 25 patients (21.2%). Among these, 18 patients carried the H1047R mutation of the kinase domain, while the remaining 7 patients carried mutations in the helical domain. mutations were associated with the estrogen receptor-positive/progesterone receptor-positive (ER/PR) group of tumors in contrast to the ER/PR group (P=0.021). Furthermore, it was observed that the mutation was associated with a poor disease prognosis. Taken together, the current study emphasized the potential of mutations as an important biomarker for breast cancer classification and the possible use of inhibitor as targeted therapy for breast cancer.