Refined mapping of loss of heterzygosity on 10q23-24 in sporadic colorectal carcinoma

Abstract

Loss of heterozygosity (LOH) of tumor suppressor gene (TSG) is believed to play a key role in carcinogenesis of colorectal cancer (CRC). In this study, we performed refined mapping of LOH on 10q23-24 region and screened the candidate TSG related to sporadic CRC. Seven fluorescent labeled polymorphic markers (encompassing D10S185 locus) were analyzed in 83 cases of colorectal carcinoma and normal tissues by PCR. PCR products were eletrophoresed on an ABI 377 DNA sequencer. GeneScan 3.1 and Genotyper 2.1 softwares were used for LOH scanning and analysis. Comparison between LOH frequency and clinicopathological factors were performed by Chi-square test. The average LOH frequency was 36.11%. The highest frequency of LOH (D10S583 locus) and the lowest (D10S205 locus) were 54.84% and 21.3%, respectively. Two obviously high LOH regions were detected: one between D10S583 locus and D10S185 locus (about 0.9 cm, 10q23.33); another flanked by D10S1709 and D10S1265 locus (about 1.5 cm, 10q24.2-24.31). Furthermore, significant difference was observed between LOH frequency and Dukes stages only on D10S1265 locus. Two obviously high frequency LOH regions, 10q23.33 and 10q24.2-24.31, were detected in sporadic CRC. Besides PTEN gene, the above two regions may harbor candidate TSG involved in development and progression of sporadic CRC.