Fusion, Disruption, and Expression of HMGA2 in Bone and Soft Tissue Chondromas

Abstract

Soft tissue and skeletal chondromas are rare entities, and only 21 cases with abnormal karyotypes have been reported. A survey of these, and 10 new cases reported herein, showed that the 12q13–15 segment is nonrandomly involved in structural rearrangements in chondromas. The HMGA2 (HMGI-C) locus in 12q15 is frequently rearranged in other benign mesenchymal tumors, and this study aimed at characterizing the expression of HMGA2 in chondromatous tumors. The material consisted of 8 soft tissue and 6 skeletal chondromas, as well as of 14 skeletal chondrosarcomas. All cases had been cytogenetically analyzed. Expression of HMGA2 could be assessed by RT-PCR in 8 chondromas and 13 chondrosarcomas. HMGA2 was expressed in 4of six soft tissue chondromas, all displaying 12q-rearrangements at cytogenetic analysis. A truncated transcript (exons 1–3), but not a full-length (exons 1–5) transcript, was detected in three of them, suggesting activation through an intragenic rearrangement. One soft tissue chondroma had a t(3;12)(q27;q15), and the RT-PCR analysis revealed an HMGA2-LPP fusion transcript, composed of HMGA2 exons 1–3 and LPP exons 9–11. An identical fusion transcript previously has been identified in lipoma and pulmonary chondroid hamartoma. In the fourth soft tissue chondroma, a full-length transcript was detected, indicating expression of at least one intact allele. Both skeletal chondromas expressed HMGA2. In one of them, a full-length transcript was detected, even though 12q was cytogenetically unaffected. A truncated or full-length transcript was found in 8 of 13 chondrosarcomas, 4 of which displayed 12q rearrangements. Possibly, cryptic rearrangements were present among the many complex marker chromosomes in the remaining 4 cases.