PIK3CA gene mutations in breast carcinoma in Malaysian patients.
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.
Ching-Shian Leong
Vincent
V
Institute of Bioscience, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, 43400 UPM Serdang, Selangor, Malaysia.
Jabal
Mohd Faizal
MF
Leong
Pooi Pooi
PP
Abdullah
Maizaton Atmadini
MA
Gul
Yunus Alif
YA
Seow
Heng Fong
HF
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
D019869:Phosphatidylinositol 3-Kinases; D058534:Class I Phosphatidylinositol 3-Kinases; C484760:PIK3CA protein, human