PIK3C Agene mutations in breast carcinoma in Malaysian patients

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 h...

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Main Authors: Leong, Vincent Ching-Shian, Jabal, Mohd Faizal, Leong, Pooi Pooi, Abdullah, Maizaton Atmadini, Gul, Yunus Alif, Seow, Heng Fong
Format: Article
Language:English
English
Published: Elsevier 2008
Subjects:
Online Access:http://psasir.upm.edu.my/id/eprint/16222/
http://psasir.upm.edu.my/id/eprint/16222/1/PIK3C%20Agene%20mutations%20in%20breast%20carcinoma%20in%20Malaysian%20patients.pdf
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author Leong, Vincent Ching-Shian
Jabal, Mohd Faizal
Leong, Pooi Pooi
Abdullah, Maizaton Atmadini
Gul, Yunus Alif
Seow, Heng Fong
author_facet Leong, Vincent Ching-Shian
Jabal, Mohd Faizal
Leong, Pooi Pooi
Abdullah, Maizaton Atmadini
Gul, Yunus Alif
Seow, Heng Fong
author_sort Leong, Vincent Ching-Shian
building UPM Institutional Repository
collection Online Access
description 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.
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spelling upm-162222015-10-05T07:43:18Z http://psasir.upm.edu.my/id/eprint/16222/ 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 Seow, Heng Fong 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. Elsevier 2008-12 Article PeerReviewed application/pdf en http://psasir.upm.edu.my/id/eprint/16222/1/PIK3C%20Agene%20mutations%20in%20breast%20carcinoma%20in%20Malaysian%20patients.pdf 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 http://www.sciencedirect.com/science/article/pii/S0165460808004603 Breast Neoplasms - Malaysia Breast - Cancer - Treatment Breast - Cancer - Diagnosis 10.1016/j.cancergencyto.2008.07.005 English
spellingShingle Breast Neoplasms - Malaysia
Breast - Cancer - Treatment
Breast - Cancer - Diagnosis
Leong, Vincent Ching-Shian
Jabal, Mohd Faizal
Leong, Pooi Pooi
Abdullah, Maizaton Atmadini
Gul, Yunus Alif
Seow, Heng Fong
PIK3C Agene mutations in breast carcinoma in Malaysian patients
title PIK3C Agene mutations in breast carcinoma in Malaysian patients
title_full PIK3C Agene mutations in breast carcinoma in Malaysian patients
title_fullStr PIK3C Agene mutations in breast carcinoma in Malaysian patients
title_full_unstemmed PIK3C Agene mutations in breast carcinoma in Malaysian patients
title_short PIK3C Agene mutations in breast carcinoma in Malaysian patients
title_sort pik3c agene mutations in breast carcinoma in malaysian patients
topic Breast Neoplasms - Malaysia
Breast - Cancer - Treatment
Breast - Cancer - Diagnosis
url http://psasir.upm.edu.my/id/eprint/16222/
http://psasir.upm.edu.my/id/eprint/16222/
http://psasir.upm.edu.my/id/eprint/16222/
http://psasir.upm.edu.my/id/eprint/16222/1/PIK3C%20Agene%20mutations%20in%20breast%20carcinoma%20in%20Malaysian%20patients.pdf