Relationship between CpG island methylator phenotype and genetic instability in sporadic colorectal cancer

OBJECTIVE: To explore the relationship between CpG island methylator phenotype(CIMP) and genetic instability in sporadic colorectal cancer(SCRC). METHODS: Seventy-one SCRC patients were enrolled in this study. Promotor methylation status of five genes including P14(ARF ), hMLH1, P16(INK4a), MGMT and MINT1 was detected with methylation specific PCR to confirm CIMP. Microsatellite instability (MSI) status was evaluated with two microsatellite loci of BAT25 and BAT26, and the ploidy was detected with flow cytometry. The association between CIMP and MSI as well as chromosomal instability(CIN) was examined. RESULTS: The positive rates of CIMP, MSI and aneuploidy were 21.1% (15/71), 9.9% (7/71) and 73.5% (50/68) respectively. The positive rate of MSI in positive CIMP patients was higher than that in negative CIMP ones, but the difference was not significant (20.0% vs 7.1%,P=0.158). The positive rate of MSI was 57.1% in patients with hMLH1 gene promotor hypermethylation, which was significantly higher than that (4.7%) in patients without hMLH1 gene promotor hypermethylation (P=0.001). SCRCs with positive CIMP displayed significant inclination of diploidy (P=0.003). The positive rate of diploidy among SCRCs with CIMP was 61.5% while only 18.2% of cases without CIMP demonstrated diploid. CONCLUSIONS: SCRCs with positive CIMP are significantly more likely to be diploid. Simultaneous multiple genes hypermethylation represented by CIMP may be an epigenetic mechanism competing with the genetic mechanism of CIN.