Studies of allelic loss in thyroid tumors reveal major differences in chromosomal instability between papillary and follicular carcinomas

Abstract

Loss of heterozygosity (LOH) studies have been used to identify sites harboring tumor suppressor genes involved in tumor initiation or progression. Previous reports have suggested that regions within chromosomes 3p, 11q, 2p, 2q, 10q, and 1p may be frequently deleted in human follicular thyroid cell tumors. We have extended the analysis of these and other selected regions to 65 paired thyroid tumor tissues. Twenty-four were follicular adenomas, 30 were papillary carcinomas, 10 were follicular carcinomas, and 1 was an anaplastic carcinoma. Sixty percent of the follicular carcinomas, 33% of the follicular adenomas, and 23% of the papillary carcinomas presented LOH at least at 1 site. Fifty percent of the follicular carcinomas showed 2 or more chromosome arms affected by deletions, whereas just 1 of the 24 follicular adenomas and none of the papillary carcinomas presented this feature. However, none of the specific loci examined had a rate of LOH greater than 33%, even in follicular carcinomas. This prompted us to place our findings into a broader context, and we, therefore, performed a meta analysis of all published studies of LOH in follicular thyroid neoplasms. There was a phenotype dependency in the overall rate of LOH, with no specific region displaying a particularly high prevalence. Most notably, by contrast to follicular carcinomas, papillary carcinomas had exceedingly low rates of LOH. Thus, there is a sharp distinction between the two major forms of differentiated thyroid cancer in their tendency to lose genetic material. This probably results from a fundamental difference in mechanisms controlling chromosomal stability in these two forms of cancers that in all likelihood has implications for tumor behavior and prognosis.