Loss of heterozygosity of chromosome 22 in sporadic colorectal carcinoma / 中华消化杂志

ABSTRACT

Objective The loss of heterozygosity (LOH) on tumor suppressor genes is believed to play a key role in the carcinogenesis of colorectal cancer. When LOH occurs at a tumor suppressor gene locus where one of the alleles is already abnormal, it can result in neoplastic transformation. In this study, we analyzed the LOH on the chromosome 22 in sporadic colorectal cancer to identify additional loci involved in colorectal tumorigenesis. Methods Six polymorphic microsatellite markers were analyzed in 83 cases of colorectal cancer and normal tissue DNA by PCR. PCR products were eletrophoresed on an ABI Prism 377 DNA sequencer; Genescan 3.1 and Genotype 2.1 software were used for LOH scanning and analysis. Comparison between LOH frequency and clinicopathological data were performed by ? 2 test. Results The average LOH frequency on chromosome 22 was 27.27%. The region between markers D22S280 and D22S274 (22q12.2-q13.33) exhibited relatively high LOH frequency. The two highest LOH loci with frequencies of 35.09% and 34.04% was identified on D22S280 (22q12.2-q12.3) and D22S274 (22q13.32-q13.33). On D22S274 locus, LOH frequency of rectal cancer was 50% (9/18), which was higher than that of proximal colon cancer (12%, 2/17) ( P =0.018). The frequency of distal colon cancer was 42% (5/12), also higher than that of proximal colon cancer. But there was no statistical significance. Putting both the tumors in distal colon and rectum together into consideration, the frequency, 47% (14/30), was higher than that of proximal colon cancer ( P = 0.015 ),suggested the mechanism of carcinogenesis was different in both groups.Conclusion This study provided evidence for the involvement of putative tumor suppressor genes related to the sporadic colorectal carcinoma on chromosome 22q. The tumor suppressor gene(s) might locate on the 22q12.2-q12.3 and/or 22q13.32 -q13.33.