Chromosomal imbalances associated with anaplastic transformation of follicular thyroid carcinomas.

The genetic alterations that underlie the progression of follicular thyroid carcinoma towards anaplasia are still largely uncharacterised. We compared the Comparative Genomic Hybridization (CGH) profiles of 20 follicular (FTCs), 12 poorly differentiated (PDTCs) and seven anaplastic thyroid carcinomas (ATCs), in order to identify the chromosomal imbalances potentially associated with cancer progression. We found: (i) when considering that a 'direct' transformation of FTC towards anaplasia occurs, the defined significantly important alterations were the increase of gains at 3q (P<0.05) and 20q (P<0.01), and the increase of losses at 7q (P<0.05) and Xp (P<0.01); (ii) regarding poorly differentiated carcinomas as an intermediate independent entity in the anaplastic transformation of follicular cancers, evidenced as important alterations towards anaplasia, were the proportional decrease in copy sequences at 7p, 7q, 12q and 13q resulting from the significant decrease of DNA gains at 7p and 12q (P<0.05), and the significant increase of losses at 7q and 13q (P<0.05). These results unveil the chromosomal regions where genes of interest in thyroid anaplastic transformation are to be located, and demonstrate that different gene dosage copy sequence imbalances are associated to the 'direct' pathway of transformation of follicular into anaplastic cancers and to the progressive FTC --> PDTC --> ATC pathway.