Loss of heterozygosity analysis of long arm of chromosome 4 in sporadic colorectal carcinoma

OBJECTIVE:To search related tumor supressor genes(TSG)through high loss of heterozygosity(LOH)loci on the long arm of the 4th chrosomose of colorectal cancer.METHODS:Thirthteen fluorescent labeled polymorphic markers were analyzed in 83 cases of colorectal carconoma and normal tissue DNA by PCR.PCR products were eletrophoresed on an ABI 377 DNA sequencer.Genescan 3.1 and Genotype 2.1 software were used for LOH scanning and analysis.Comparison between LOH frequency and clinicopathological factors was performed by Chi-square test.RESULTS:The average LOH frequency was 28.56% on 4q.Two obvious high LOH regions were detected:one between D4S3000 locus and D4S2915 locus(4q12-21.1);another flanked by D4S407 and D4S2939 locus(4q25-31.1).Furthermore,significant difference of LOH was observed between tumor larger than 5cm in diamerter and one less than 5cm on D4S3018 locus(56% vs 13.79%,P=0.01).LOH was significantly higher in liver metasteasis patients than in non-liver metasteasis on D4S1534 locus(80% vs 17.25%,P=0.012).CONCLUSION:Two obvious high frequency LOH regions:4q12-21.1,4q25-31.1 may be harbor candidate TSG involved in tumorigenesis and progression of sporadic CRC.