Missense mutations in MLH1, MSH2, KRAS, and APC genes in colorectal cancer patients in malaysia

Nor Azian Abdul Murad, Zulhabri Othman, Melati Khalid, Zuraini Abdul Razak, Rosniza Hussain, Sukumar Nadesan, Ismail Sagap, Isa Mohamed Rose, Wan Zurinah Wan Ngah, A. Rahman A. Jamal

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

Background: Colorectal cancer (CRC) is the third most common cancer worldwide with approximately 1 million cases diagnosed annually. In Malaysia, CRC is the second most common cancer in women and ranked first in men. The underlying cause of CRC remains unknown. Aims: The aim of this study was to analyze the mutations in genes involved in CRC including MLH1, MSH2, KRAS, and APC genes. Methods: A total of 76 patients were recruited. We used the polymerase chain reaction-denaturing high-performance liquid chromatography for the detection of mutations in the mismatch repair (MMR) and APC genes and the PCR single-strand conformation polymorphism for screening of the KRAS gene mutations. Results: We identified 17 types of missense mutations in 38 out of 76 patients in our patients. Nine mutations were identified in the APC gene, five mutations were detected in the KRAS gene, and two mutations were identified in the MSH2 gene. Only one mutation was identified in MLH1. Out of these 17 mutations, eight mutations (47 %) were predicted to be pathogenic. Seven patients were identified with multiple mutations (3: MSH2 and KRAS, 1: KRAS and APC, 1: MLH1 and APC, 2: APC and APC). Conclusions: We have established the PCR-DHPLC and PCR-SSCP for screening of mutations in CRC patients. This study has given a snapshot of the spectrum of mutations in the four genes that were analyzed. Mutation screening in patients and their family members will help in the early detection of CRC and hence will reduce mortality due to CRC.

Original languageEnglish
Pages (from-to)2863-2872
Number of pages10
JournalDigestive Diseases and Sciences
Volume57
Issue number11
DOIs
Publication statusPublished - Nov 2012

Fingerprint

APC Genes
Malaysia
Missense Mutation
Colorectal Neoplasms
Mutation
Polymerase Chain Reaction
Genes
Single-Stranded Conformational Polymorphism
DNA Mismatch Repair
Early Detection of Cancer

Keywords

  • APC
  • Colorectal cancer
  • KRAS
  • MLH1
  • MSH2
  • Mutation

ASJC Scopus subject areas

  • Gastroenterology
  • Physiology

Cite this

Missense mutations in MLH1, MSH2, KRAS, and APC genes in colorectal cancer patients in malaysia. / Abdul Murad, Nor Azian; Othman, Zulhabri; Khalid, Melati; Razak, Zuraini Abdul; Hussain, Rosniza; Nadesan, Sukumar; Sagap, Ismail; Rose, Isa Mohamed; Ngah, Wan Zurinah Wan; A. Jamal, A. Rahman.

In: Digestive Diseases and Sciences, Vol. 57, No. 11, 11.2012, p. 2863-2872.

Research output: Contribution to journalArticle

Abdul Murad, Nor Azian ; Othman, Zulhabri ; Khalid, Melati ; Razak, Zuraini Abdul ; Hussain, Rosniza ; Nadesan, Sukumar ; Sagap, Ismail ; Rose, Isa Mohamed ; Ngah, Wan Zurinah Wan ; A. Jamal, A. Rahman. / Missense mutations in MLH1, MSH2, KRAS, and APC genes in colorectal cancer patients in malaysia. In: Digestive Diseases and Sciences. 2012 ; Vol. 57, No. 11. pp. 2863-2872.
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abstract = "Background: Colorectal cancer (CRC) is the third most common cancer worldwide with approximately 1 million cases diagnosed annually. In Malaysia, CRC is the second most common cancer in women and ranked first in men. The underlying cause of CRC remains unknown. Aims: The aim of this study was to analyze the mutations in genes involved in CRC including MLH1, MSH2, KRAS, and APC genes. Methods: A total of 76 patients were recruited. We used the polymerase chain reaction-denaturing high-performance liquid chromatography for the detection of mutations in the mismatch repair (MMR) and APC genes and the PCR single-strand conformation polymorphism for screening of the KRAS gene mutations. Results: We identified 17 types of missense mutations in 38 out of 76 patients in our patients. Nine mutations were identified in the APC gene, five mutations were detected in the KRAS gene, and two mutations were identified in the MSH2 gene. Only one mutation was identified in MLH1. Out of these 17 mutations, eight mutations (47 {\%}) were predicted to be pathogenic. Seven patients were identified with multiple mutations (3: MSH2 and KRAS, 1: KRAS and APC, 1: MLH1 and APC, 2: APC and APC). Conclusions: We have established the PCR-DHPLC and PCR-SSCP for screening of mutations in CRC patients. This study has given a snapshot of the spectrum of mutations in the four genes that were analyzed. Mutation screening in patients and their family members will help in the early detection of CRC and hence will reduce mortality due to CRC.",
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T1 - Missense mutations in MLH1, MSH2, KRAS, and APC genes in colorectal cancer patients in malaysia

AU - Abdul Murad, Nor Azian

AU - Othman, Zulhabri

AU - Khalid, Melati

AU - Razak, Zuraini Abdul

AU - Hussain, Rosniza

AU - Nadesan, Sukumar

AU - Sagap, Ismail

AU - Rose, Isa Mohamed

AU - Ngah, Wan Zurinah Wan

AU - A. Jamal, A. Rahman

PY - 2012/11

Y1 - 2012/11

N2 - Background: Colorectal cancer (CRC) is the third most common cancer worldwide with approximately 1 million cases diagnosed annually. In Malaysia, CRC is the second most common cancer in women and ranked first in men. The underlying cause of CRC remains unknown. Aims: The aim of this study was to analyze the mutations in genes involved in CRC including MLH1, MSH2, KRAS, and APC genes. Methods: A total of 76 patients were recruited. We used the polymerase chain reaction-denaturing high-performance liquid chromatography for the detection of mutations in the mismatch repair (MMR) and APC genes and the PCR single-strand conformation polymorphism for screening of the KRAS gene mutations. Results: We identified 17 types of missense mutations in 38 out of 76 patients in our patients. Nine mutations were identified in the APC gene, five mutations were detected in the KRAS gene, and two mutations were identified in the MSH2 gene. Only one mutation was identified in MLH1. Out of these 17 mutations, eight mutations (47 %) were predicted to be pathogenic. Seven patients were identified with multiple mutations (3: MSH2 and KRAS, 1: KRAS and APC, 1: MLH1 and APC, 2: APC and APC). Conclusions: We have established the PCR-DHPLC and PCR-SSCP for screening of mutations in CRC patients. This study has given a snapshot of the spectrum of mutations in the four genes that were analyzed. Mutation screening in patients and their family members will help in the early detection of CRC and hence will reduce mortality due to CRC.

AB - Background: Colorectal cancer (CRC) is the third most common cancer worldwide with approximately 1 million cases diagnosed annually. In Malaysia, CRC is the second most common cancer in women and ranked first in men. The underlying cause of CRC remains unknown. Aims: The aim of this study was to analyze the mutations in genes involved in CRC including MLH1, MSH2, KRAS, and APC genes. Methods: A total of 76 patients were recruited. We used the polymerase chain reaction-denaturing high-performance liquid chromatography for the detection of mutations in the mismatch repair (MMR) and APC genes and the PCR single-strand conformation polymorphism for screening of the KRAS gene mutations. Results: We identified 17 types of missense mutations in 38 out of 76 patients in our patients. Nine mutations were identified in the APC gene, five mutations were detected in the KRAS gene, and two mutations were identified in the MSH2 gene. Only one mutation was identified in MLH1. Out of these 17 mutations, eight mutations (47 %) were predicted to be pathogenic. Seven patients were identified with multiple mutations (3: MSH2 and KRAS, 1: KRAS and APC, 1: MLH1 and APC, 2: APC and APC). Conclusions: We have established the PCR-DHPLC and PCR-SSCP for screening of mutations in CRC patients. This study has given a snapshot of the spectrum of mutations in the four genes that were analyzed. Mutation screening in patients and their family members will help in the early detection of CRC and hence will reduce mortality due to CRC.

KW - APC

KW - Colorectal cancer

KW - KRAS

KW - MLH1

KW - MSH2

KW - Mutation

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