Recurrent Fusion of the Genes for High-mobility Group AT-hook 2 (HMGA2) and Nuclear Receptor Co-repressor 2 (NCOR2) in Osteoclastic Giant Cell-rich Tumors of Bone.

Background/Aim: Chimeras involving the highmobility group AT-hook 2 gene (HMGA2 in 12q14.3) have been found in lipomas and other benign mesenchymal tumors. We report here a fusion of HMGA2 with the nuclear receptor co-repressor 2 gene (NCOR2 in 12q24.31) repeatedly found in tumors of bone and the first cytogenetic investigation of this fusion. Materials and Methods: Six osteoclastic giant cell-rich tumors were investigated using G-banding, RNA sequencing, reverse transcription polymerase chain reaction, Sanger sequencing, and fluorescence in situ hybridization. Results: Four tumors had structural chromosomal aberrations of 12q. The pathogenic variant c.103_104GG>AT (p.Gly35Met) in the H3.3 histone A gene was found in a tumor without 12q aberration. Inframe HMGA2–NCOR2 fusion transcripts were found in all tumors. In two cases, the presence of an HMGA2–NCOR2 fusion gene was confirmed by FISH on metaphase spreads. Conclusion: Our results demonstrate that a subset of osteoclastic giant cell-rich tumors of bone are characterized by an HMGA2–NCOR2 fusion gene. [ABSTRACT FROM AUTHOR]