title: PIK3CA gene mutations in breast carcinoma in Malaysian patients.
abstract: Somatic mutations of phosphoinositide-3-kinase, catalytic, alpha; PIK3CA gene have been reported in several types of human cancers. The majority of the PIK3CA mutations 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 p110alpha. These hot spot mutations lead to a gain of function in PI3 K signaling. We aimed to determine the frequency of PIK3CA mutations in the three most common Malaysian cancers. In this study, we assessed the genetic alterations in the PIK3CA gene in a series of 20 breast carcinomas, 24 colorectal carcinomas, 27 nasopharyngeal carcinomas (NPC), and 5 NPC cell lines. We performed mutation analysis of the PIK3CA gene 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 PIK3CA mutations was present in Malaysian breast cancers as compared to colorectal and nasopharyngeal tumor tissues. Our findings also indicate that PIK3CA mutations 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.
authors.affiliation: Institute of Bioscience, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, 43400 UPM Serdang, Selangor, Malaysia.
authors.forename: Vincent
authors.initials: V
authors.lastname: Ching-Shian Leong
authors.forename: Mohd Faizal
authors.initials: MF
authors.lastname: Jabal
authors.forename: Pooi Pooi
authors.initials: PP
authors.lastname: Leong
authors.forename: Maizaton Atmadini
authors.initials: MA
authors.lastname: Abdullah
authors.forename: Yunus Alif
authors.initials: YA
authors.lastname: Gul
authors.forename: Heng Fong
authors.initials: HF
authors.lastname: Seow
mesh_terms: D001943:Breast Neoplasms / Q000235:genetics* / Q000378:metabolism; D045744:Cell Line, Tumor; D058534:Class I Phosphatidylinositol 3-Kinases; D015179:Colorectal Neoplasms / Q000235:genetics / Q000378:metabolism; D004252:DNA Mutational Analysis; D006801:Humans; D008296:Malaysia; D009154:Mutation; D009303:Nasopharyngeal Neoplasms / Q000235:genetics / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: D019869:Phosphatidylinositol 3-Kinases; D058534:Class I Phosphatidylinositol 3-Kinases; C484760:PIK3CA protein, human