Chromosomal imbalances associated with anaplastic transformation of follicular thyroid carcinomas

Abstract

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 (Po0.05) and 20q (Po0.01), and the increase of losses at 7q (Po0.05) and Xp (Po0.01); (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 (Po0.05), and the significant increase of losses at 7q and 13q (Po0.05). 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.

Poorly differentiated and anaplastic thyroid carcinomas: chromosomal and oligo-array profile of five new cell lines

“…Comparison of our PDTC and ATC CGH results with previously reported data (Hemmer et al, 1999;Wilkens et al, 2000;Wreesmann et al, 2002;Rodrigues et al, 2004) revealed that all imbalances, described as frequently occurring in the literature, were also observed in the cell lines.…”

“…The chromosomal gains and losses observed for each of the cell lines and respective primary tumours were represented in an excel table (CGH supplementary data). Analysis of these data allowed to verify that although CGH alterations observed in the cell lines were not identical to the ones found in primary tumours, they presented major similarities, indicating that these cell lines largely reflect their primary tumour major cytogenetic imbalances.Comparison of our PDTC and ATC CGH results with previously reported data (Hemmer et al, 1999;Wilkens et al, 2000;Wreesmann et al, 2002;Rodrigues et al, 2004) revealed that all imbalances, described as frequently occurring in the literature, were also observed in the cell lines. …”

“…Overall, gains of DNA sequences were more frequent than losses. High-level amplification regions were observed in the following cell lines: in T235 at regions 3q24-qter, 7q11.2-q22, 12pter-p11 and chromosome 20; in T238 at 18q21; and in T241 at 5pter-p12, 7pter-p21, 14q10-qter, and 20p11.2-qter ( Figure 2B -D).Comparative genomic hybridisation of the corresponding primary tumours have been performed and reported previously (Rodrigues et al, 2004). The chromosomal gains and losses observed for each of the cell lines and respective primary tumours were represented in an excel table (CGH supplementary data).…”

“…Comparative genomic hybridisation of the corresponding primary tumours have been performed and reported previously (Rodrigues et al, 2004). The chromosomal gains and losses observed for each of the cell lines and respective primary tumours were represented in an excel table (CGH supplementary data).…”

“…At variance, the genetic information concerning PDTC and ATC is very limited. Only 27 PDTC have been evaluated by comparative genomic hybridisation (CGH) analysis, and as far as we are aware, there are no microarray studies on this entity (Wreesmann et al, 2002;Rodrigues et al, 2004). In ATC, it was demonstrated that TP53 (Wynford- Thomas, 1997) and b-catenin (Garcia-Rostan et al, 1999) mutations as well as the overexpression of OEATC1 (Mizutani et al, 2005) and AURKB (Sorrentino et al, 2005) were associated with ATC phenotype.…”