Rearrangement of PPARγ in a thyroid adenoma without 2q13 involvement: evidence for a breakpoint hot spot within the close surrounding of PPARγ?

In benign thyroid tumours main cytogenetic subgroups characterized by trisomy 7 and by rearrangements of either 19q13 or 2p21, respectively, have been described. Recently, we had been able to describe a novel gene called THADA (thyroid adenoma associated) affected by translocations involving chromosomal band 2p21. THADA is rearranged in benign thyroid tumors leading to a THADA-fusion gene in which the 3'-part is truncated and ectopic sequences derived from the translocation partners are fused to THADA. Other fusion genes found in thyroid tumours are RET/PTC2 and PAX8/PPARγ. The latter is caused by a translocation t(2;3)(q13;p25). Apart from PAX8/PPARγ rearrangements the chromosomal region 3p25 where PPARγ maps to is frequently affected by rearrangements in different thyroid tumours including papillary carcinomas, follicular carcinomas, and follicular adenomas, indicating that this region seems to be a breakpoint hot spot region.

Here we present molecular-cytogenetic and cytogenetic investigations on a follicular thyroid adenoma with a t(2;20;3)(p21;q11.2;p25). In this case an intronic sequence of PPARγ is fused to exon 28 of THADA. With BAC clones containing the genomic sequence of PPARγ we could confirm the breakpoint localization to intron 2 of PPARγ in fluorescence in situ hybridization studies. Our findings suggest that the close surrounding of PPARγ is a breakpoint hot spot region, leading to recurrent alterations of this gene in tumours of the thyroid including follicular carcinomas as well as follicular adenomas without involvement of PAX8.