Abstract
We carried out this study to distinguish whether colon tumor progression is linked to the accumulation of mutations and deletions in tumor suppressor genes such as DCC (deleted in colorectal cancer) and APC (adenomatous polyposis coli) whose chromosomal loci are at 18q and 5q respectively. We analyzed 80 sporadic colorectal tumors (B and C stages) for 18q LOH and 5q LOH using the polymorphic DNA markers D18S67 (proximal to DCC gene), D18S58 (distal to DCC gene) and D5S82 (APC gene). DNA from paired tumor and normal tissue at these loci was amplified by PCR. Amplification products were electrophoresed on 6% denaturing polyacrylamide gels. Of a total of 68 (85%) informative cases, 24 (35%) showed allelic losses at either or both of the two 18q chromosomal loci examined. In the locus tested for chromosome 5q, 54 (75%) cases were informative with 22 (41%) showing allelic loss. Median survival time (mst) was 53.5 months in patients with stage B tumors with 18q LOH in comparison with 71 months for those without 18q LOH. Similarly, mst in patients with stage B tumors with 5q LOH was 56 months in contrast to 89 months for those without 5q LOH. No differences in survival were seen for either 18q LOH or 5q LOH in stage C. Our results suggest that LOH at 18q and 5q confer poor survival in stage B colorectal cancer.
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