Refinement Of High Heterozygosity Loss On Chromosome In Sporadic Colorectal Cancer

AIM: To refine the loss of heterozygosity on chromosome 3q24-25, 5pl5 5ql4, 7q21-22, 20qll -13, 22ql2 and identify the new tumor suppressor genes in colorectal tumorigenesis.METHODS: 13, 16, 15, 10, 6 polymorphic microsatellite markers were analyzed on chromosome 3, 5, 7, 20, 22 respectively and another 6, 6, 7, 5, 10, 7 markers were applied respectively on chromosome 3q24-25, 5pl5, 5ql4, 7q21-22, 20qll -13, 22ql2 in 83 cases of colorectal and normal DNA by PCR. PCR products were eletrophoresed on an ABI 377 DNA sequencer. Genescan3. land Genotype 2. 1 software were used for LOH scanning and analysis.RESULTS: We observed 2 distinct regions of frequent allelic deletions on Chromosome 5, 5pl5 and 5ql4, another 6 polymorphric microsatellite markers were applied to 5pl5 and the minimal region of frequrent loss of heterozygosity was established on 5pl5 spanning the D5S416 locus, another 7 polymorphric microsatellite markers were applied to 5ql4 and the three minimal regions of frequrent loss of heterozygosity was established on 5ql4: spanning the D5S428 locus, spanning the D5S64K D5S2094 loci and spanning the D5S617. D5S2495> D5S2103 loci; 2 distinct regions of frequent allelic deletions on Chromosome 3, 3pl4 and 3q24-25, were found, another 6 polymorphric microsatellite markers were applied to 3q24-25 and the minimal region of frequrent loss of heterozygosity was established on it spanning the D3S1279 locus; we observed a distinct region of frequent allelic deletions on Chromosome 7, that is to say 7q21-22, another 5 polymorphric microsatellite markers were applied to 7q21-22 and the minimal region of frequrent loss of heterozygosity was established on it spanning the D7S657and D7S646 loci; A distinct region of frequent allelic deletions on Chromosome 20, 20qll-13, was found, another 10 polymorphric microsatellite markers were applied to 20qll-13 and the two minimal regions of frequrent loss of heterozygosity were established on it, oneis about 2-3cM spanning the D20S878 locus,the other is about l-2cM spanning D20S107; We also observed a distinct region of frequent allelic deletions on Chromosome 22, 22ql2, another 7 polymorphric microsatellite markers were applied to 22ql2 and the three minimal regions of frequrent loss of heterozygosity was established on it: spanning the D22S1154, D22S1144 loci, spanning the D22S1150, 22S1176 loci and spanning D22S280, D22S1162.CONCLUSION: Through our detailed deletion mapping studies, we have found several critical and precise location of deletions on chromosome 3, 5, 7, 20, 22 which must contain more unknown tumor suppressor genes on colorectal cancer.