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Microallelotyping defines the sequence and tempo of alleiic losses at tumour suppressor gene loci during colorectal cancer progression

Abstract

Microallelotyping of many regions from individual colorectal tumours was used to determine the sequence and tempo of alleiic loss on 5q, 17p and 18q during neoplastic progression. No alleiic losses were found in normal tissues surrounding colorectal neoplasms, but losses occurred abruptly on 5q at the transition from normal colonic epithelium to the benign adenoma, and on 17p at the transition from adenoma to carcinoma, indicating an essential role for these losses in tumour progression. Alleiic losses were uniform throughout extensively microdissected benign adenomas and carcinomas. However, substantial alleiic heterogeneity was found in high–grade dysplasia, the transition lesion between adenoma and carcinoma. Thus, alleiic losses on 5q and 17p are associated with abrupt waves of clonal neoplastic expansion, and high–grade dysplasia is characterized by a high degree of alleiic heterogeneity.

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Boland, C., Sato, J., Appelman, H. et al. Microallelotyping defines the sequence and tempo of alleiic losses at tumour suppressor gene loci during colorectal cancer progression. Nat Med 1, 902–909 (1995). https://doi.org/10.1038/nm0995-902

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