MICROALLELOTYPING DEFINES THE SEQUENCE AND TEMPO OF ALLELIC LOSSES ATTUMOR-SUPPRESSOR GENE LOCI DURING COLORECTAL-CANCER PROGRESSION

Microallelotyping of many regions from individual colorectal tumours w as used to determine the sequence and tempo of allelic loss on 5q, 17p and 18q during neoplastic progression. No allelic losses were found i n normal tissues surrounding colorectal neoplasms, but losses occurred abruptly on 5q at the transition from normal colonic epithelium to th e benign adenoma, and on 17p at the transition from adenoma to carcino ma, indicating an essential role for these losses in tumour progressio n. Allelic losses were uniform throughout extensively microdissected b enign adenomas and carcinomas. However, substantial allelic heterogene ity was found in high-grade dysplasia, the transition lesion between a denoma and carcinoma. Thus, allelic losses on 5q and 17p are associate d with abrupt waves of clonal neoplastic expansion, and high-grade dys plasia is characterized by a high degree of allelic heterogeneity.