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DNA extracted from familial and sporadic colorectal neoplasms was compared with constitutional DNA using a range of hypervariable locus specific probes to assess the extent of allele loss during conversion to malignancy. Chromosome 5 allele loss was observed in 23% of carcinoma samples, as previously found by others. However, we have been able to show for the first time loss of the D5S43 locus on chromosome 5 in adenomas from three patients, two of whom had the precancerous condition adenomatous polyposis coli (APC). These results suggest significant genetic changes involving chromosome 5 are occurring in benign adenomas. Probes for chromosome 1 (loci D1S7 and D1S8) and for chromosome 7 (loci D7S21 and D7S22) revealed no notable alterations in the adenoma samples. Complete loss of alleles for loci on chromosome 7 was not observed in carcinomas but reduced intensity of one parental allele was found in three specimens one of which was known to have multiple copies of this chromosome. Results using probes for chromosome 1 suggest that deletion of the D1S7 or D1S8 loci is not a common event in colorectal carcinogenesis. Loss of chromosome 5 alleles in adenomas from APC patients provides evidence in support of Knudson's hypothesis.

Chromosome 5 allele loss in familial and sporadic colorectal adenomas