Allelotyping of anaplastic thyroid carcinoma: Frequent allelic losses on 1q, 9p, 11, 17, 19p, and 22q

Abstract

Little is known about the genetic mechanisms behind the genesis of anaplastic thyroid carcinoma. This is among the most virulent of all human malignancies, and it is believed to result most often from transformation of differentiated thyroid carcinomas of the papillary type. So far, TP53 and beta-catenin mutations are the only genetic alterations that have been implicated in its pathogenesis. To identify loci of other potential tumor suppressor genes, we carried out a genome-wide allelotyping study using 39 microsatellite markers representing all nonacrocentric autosomal arms, in a panel of 21 anaplastic thyroid carcinomas. Frequent allelic losses were identified in 1q (40%), 9p (58%), 11p (33%), 11q (33%), 17p (44%), 17q (43%), 19p (36%), and 22q (38%). Deletion mapping of chromosome arms with the most frequent allelic losses (frequencies above 40%) localized the commonly deleted region to 1q31-42, 9p21-22, 17p12-ter, and 17q21.1-22. The mean frequency of loss of heterozygosity on all arms tested was 20%, and the mean fractional allelic loss among the cancers examined was 0.20. These findings defined a sharp distinction between anaplastic thyroid carcinomas and papillary thyroid carcinomas, because the latter do not tend to show losses at the same loci. Frequent allelic losses at multiple loci may implicate chromosomal instability as an important factor in the development of anaplastic thyroid carcinomas. Genes Chromosomes Cancer 27:244-251, 2000.