DNA alterations of microsatellite DNA, p53, APC and K‐ras in Chinese colorectal cancer patients

Abstract

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. 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. 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.