Truncation and fusion of HMGA2 in lipomas with rearrangements of 5q32-->q33 and 12q14-->q15.

Chromosome segment 12q13-->q15 recombines with many different chromosome bands in lipomas and at least ten recurrent translocations have been identified. The HMGA2 gene is often rearranged, but little is known about the molecular consequences at other breakpoints. Fusion genes between HMGA2 (12q14-->q15) and LPP (3q27-->q28), LHFP (13q12) and CMKOR1 (2q37) have been reported. In the present study, eight lipomas with rearrangements involving chromosome bands 12q14-->q15 and 5q32-->q33 were analyzed. In chromosome 5, five of the cases had a breakpoint in the 5' part of EBF in 5q33, while three cases had breakpoints located about 200 kb 3' of EBF. In chromosome 12, the breakpoints clustered to the region of HMGA2. Four cases had breaks within the gene and four had breaks 5' to HMGA2 where the gene BC058822 is located. Two versions of an HMGA2/EBF fusion transcript were detected in one case; one transcript was in frame and the other out of frame. Identical EBF/BC058822 fusion transcripts, seen in two cases, one of which also had the HMGA2/EBF transcript, were out of frame and resulted in truncation of EBF. Since EBF and HMGA2 have different orientations, the findings must be explained by complex aberrations including multiple breaks. The combined data indicate that the pathogenetically significant event is fusion, truncation or transcriptional activation of HMGA2, but it can not be excluded that EBF, which has been implicated in adipogenesis, contributes to the tumor development.