Loss of heterozygosity of the long arm of chromosome 7 in follicular and anaplastic thyroid cancer, but not in papillary thyroid cancer

Papillary thyroid cancer (PTC), but neither the follicular nor the anaplast ic histotype [follicular thyroid cancer (FTC), anaplastic thyroid cancer (A TC)], overexpresses simultaneously the protooncogene HGF (hepatocyte growth factor) and its receptor HGF-R (or c-met). Because 1) HGF and c-met map to chromosome 7q21 and 7q31, respectively, 2) FTC loses genetic material at m ultiple loci with a frequency much higher than PTC, and 3) loss of heterozy gosity (LOH) on 7q has been previously found in various tumors, we tested t he hypothesis that both FTC and ATC, but not PTC, could harbor LOH in segme nts of 7q encompassing the loci for HGF and c-met. We screened 6 normal thyroids, 10 colloid nodules, 10 follicular hyperplasi as, 10 oncocytic adenomas, 10 follicular adenomas (FA), 10 FTC, 6 ATC, 12 P TC using two microsatellite markers for HGF, and two for c-met. LOH for all 4 markers was found in 100% of FTC, 100% of ATC, and (for only 1 or 2 mark ers) in 10-29% of FA. This is the first demonstration of an LOH that separates both FTC and ATC f rom PTC, in the best possible manner: 100% us. 0%. Clearly, each of the two segments we have probed contains at least one tumor suppressor gene, whose inactivation is crucial for the establishment of the FTC land ATC) phenoty pe. This loss of genetic material explains why FTC and ATC, but not PTC, fa il to express both HGF and c-met. Our findings may also have immediate diag nostic application, in the context of assisting pathologists in the often d ifficult task of distinguishing FA from FTC.