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PIK3C Agene mutations in breast carcinoma in Malaysian patients

Leong, Vincent Ching-Shian , Jabal, Mohd Faizal , Leong, Pooi Pooi , Abdullah, Maizaton Atmadini , 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/S...

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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