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


OBJECTIVE
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.
UKM Medical Molecular Biology Institute (UMBI), Universiti Kebangsaan Malaysia Medical Centre (UKMMC), Jalan Yaacob Latif, 56000 Cheras, Kuala Lumpur, Malaysia.
Nor Azian
NA
Abdul Murad
Zulhabri
Z
Othman
Melati
M
Khalid
Zuraini
Z
Abdul Razak
Rosniza
R
Hussain
Sukumar
S
Nadesan
Ismail
I
Sagap
Isa
I
Mohamed Rose
Wan Zurinah
WZ
Wan Ngah
Rahman
R
Jamal
D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics*; D000368:Aged; D002851:Chromatography, High Pressure Liquid; D015179:Colorectal Neoplasms / Q000235:genetics*; D005260:Female; D017491:Genes, APC; D006801:Humans; D019656:Loss of Heterozygosity; D008296:Malaysia; D008297:Male; D008875:Middle Aged; D000070957:MutL Protein Homolog 1; D051718:MutS Homolog 2 Protein / Q000235:genetics; D020125:Mutation, Missense; D009687:Nuclear Proteins / Q000235:genetics*; D016133:Polymerase Chain Reaction; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins / Q000378:metabolism*
D048868:Adaptor Proteins, Signal Transducing; C117307:KRAS protein, human; C501486:MLH1 protein, human; D009687:Nuclear Proteins; D011518:Proto-Oncogene Proteins; C497172:MSH2 protein, human; D000070957:MutL Protein Homolog 1; D051718:MutS Homolog 2 Protein; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins