Helical and kinase domain mutations of PIK3CA, and their association with hormone receptor expression in breast cancer

Vatte,Chittibabu; Al Amri,Ali   Mohammed; Cyrus,Cyril; Chathoth,Shahanas; Alsayyah,Ahmed; Ahmad,Arafat; Akhtar,Mohammed  Shakil; Alrashidi,Nada  Fehaid; Jayaseeli,Nithya; Al Wadani,Hamed; Al Zahrani,Alhussain; Al Ali,Amein   Kadhem

doi:10.3892/ol.2019.10565

Helical and kinase domain mutations of PIK3CA, and their association with hormone receptor expression in breast cancer

Authors:
- Chittibabu Vatte
- Ali Mohammed Al Amri
- Cyril Cyrus
- Shahanas Chathoth
- Ahmed Alsayyah
- Arafat Ahmad
- Mohammed Shakil Akhtar
- Nada Fehaid Alrashidi
- Nithya Jayaseeli
- Hamed Al Wadani
- Alhussain Al Zahrani
- Amein Kadhem Al Ali
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Affiliations: Department of Biochemistry, College of Medicine, Imam Abdulrahman Bin Faisal University, Dammam 31441, Kingdom of Saudi Arabia, Department of Internal Medicine, King Fahd Hospital of the University, Imam Abdulrahman Bin Faisal University, Al‑Khobar 31952, Kingdom of Saudi Arabia, Department of Pathology, King Fahd Hospital of the University, Imam Abdulrahman Bin Faisal University, Al‑Khobar 31952, Kingdom of Saudi Arabia, Department of Surgery, King Faisal University, Hofuf, Al‑Ahsa 31982, Kingdom of Saudi Arabia, Department of Clinical Laboratories Sciences, College of Applied Medical Sciences, King Saud University, Riyadh 11362, Kingdom of Saudi Arabia
Published online on: July 4, 2019 https://doi.org/10.3892/ol.2019.10565
Pages: 2427-2433
Copyright : © Vatte et al. This is an open access article distributed under the terms of Creative Commons Attribution License [CC BY 4.0].

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Abstract

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 (PIK3CA) 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 PIK3CA 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 PIK3CA. 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. PIK3CA 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 PIK3CA mutation was associated with a poor disease prognosis. Taken together, the current study emphasized the potential of PIK3CA mutations as an important biomarker for breast cancer classification and the possible use of PIK3CA inhibitor as targeted therapy for breast cancer.

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