PIK3C Agene mutations in breast carcinoma in Malaysian patients

Leong, Vincent Ching-Shian and Jabal, Mohd Faizal and Leong, Pooi Pooi and Abdullah, Maizaton Atmadini and Gul, Yunus Alif and Seow, Heng Fong (2008) PIK3C Agene mutations in breast carcinoma in Malaysian patients. Cancer Genetics and Cytogenetics, 187 (2). pp. 74-79. ISSN 0165-4608, ESSN: 1873-4456

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Official URL: http://www.sciencedirect.com/science/article/pii/S0165460808004603

Abstract

Somatic mutations of phosphoinositide-3-kinase, catalytic, α; PIK3CAgene have been reported in several types of human cancers. The majority of the PIK3CAmutations map to the three “hot spots” — E542 K and E545 K in the helical (exon 9) and H1047R in the kinase (exon 20) domains of the p110α. These hot spot mutations lead to a gain of function in PI3 K signaling. We aimed to determine the frequency of PIK3CAmutations in the three most common Malaysian cancers. In this study, we assessed the genetic alterations in the PIK3CAgene in a series of 20 breastcarcinomas, 24 colorectal carcinomas, 27 nasopharyngeal carcinomas (NPC), and 5 NPC cell lines. We performed mutation analysis of the PIK3CAgene by genomic polymerase chain reaction (PCR) and followed by DNA direct sequencing in exons 9 and 20. No mutations were detected in any of the 24 colorectal and 27 NPC samples, but one hot spot mutation located at exon 20 was found in a NPC cell line, SUNE1. Interestingly, PIK3CA somatic mutations were present in 6/20 (30%) breast carcinomas. Two of the six mutations, H1047R, have been reported previously as a hot spot mutation. Only one out of three hot spot mutations were identified in breast tumor samples. The remaining four mutations were novel. Our data showed that a higher incidence rate of PIK3CAmutations was present in Malaysian breast cancers as compared to colorectal and nasopharyngeal tumor tissues. Our findings also indicate that PIK3CAmutations play a pivotal role in activation of the PI3 K signaling pathway in breast cancer, and specific inhibitors of PIK3CA could be useful for breast cancer treatment in Malaysia.

Item Type:Article
Subject:Breast Neoplasms - Malaysia
Subject:Breast - Cancer - Treatment
Subject:Breast - Cancer - Diagnosis
Faculty or Institute:Faculty of Medicine and Health Science
Publisher:Elsevier
DOI Number:10.1016/j.cancergencyto.2008.07.005
Altmetrics:http://www.altmetric.com/details.php?domain=psasir.upm.edu.my&doi=10.1016/j.cancergencyto.2008.07.005
ID Code:16222
Deposited By: Raja Norazlinda Raja Azenam
Deposited On:07 Aug 2012 07:14
Last Modified:31 Oct 2012 04:18

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