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DNA alterations of microsatellite DNA, p53, APC and K‐ras in Chinese colorectal cancer patients
Author(s) -
Xu XinMin,
Qian JianChang,
Cai Zhe,
Tang Tao,
Wang Peng,
Zhang KeHua,
Deng ZhouLu,
Cai JianPing
Publication year - 2012
Publication title -
european journal of clinical investigation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.164
H-Index - 107
eISSN - 1365-2362
pISSN - 0014-2972
DOI - 10.1111/j.1365-2362.2011.02641.x
Subject(s) - microsatellite instability , microsatellite , loss of heterozygosity , adenomatous polyposis coli , colorectal cancer , biology , familial adenomatous polyposis , carcinogenesis , dna mismatch repair , cancer research , microbiology and biotechnology , metastasis , cancer , genetics , gene , allele
Eur J Clin Invest 2012; 42 (7): 751–759 Abstract Background Colorectal cancer is one of the most rapidly increasing cancers in the world, and accumulation of alterations in oncogenes, tumour suppressor genes and mismatch repair (MMR) genes contributes to colorectal tumorigenesis. Thus, we investigated the alterations of 14 microsatellite loci adjacent to MMR genes, p53, adenomatous polyposis coli (APC) and K‐ras in 52 Chinese patients with colorectal cancer. Materials and Methods We performed fluorescent polymerase chain reaction and capillary electrophoresis to analyse microsatellite instability (MSI) and loss of heterozygosity (LOH) in microsatellite loci, which included a panel of nine dinucleotide repeats and the Bethesda consensus panel. Additionally, we screened for mutations in exons 4–9 of p53 and the mutation cluster region (MCR) in APC by DHPLC. Codons 12, 13 and 61 in K‐ras were analysed using direct sequencing. All variations were confirmed using clone sequencing. Results The alteration frequency of microsatellite DNA was 55·8% (29/52). Among the microsatellites, five loci exhibited MSI and another nine loci exhibited LOH. The mutation rates of p53, APC and K‐ras were 42·3%, 38·5% and 36·5%, respectively. All patients ( n = 7) with liver metastasis had a mutation in p53, APC or K‐ras. APC mutation was correlated with clinical stage and the presence of lymph node metastasis ( P = 0·001 and P = 0·006, respectively). Conclusions A total of 80·8% of Chinese patients with colorectal cancer show variations in microsatellite DNA, p53, APC or K‐ras. It appears that these microsatellite DNA alterations could be a new biomarker for colorectal cancer.