title: 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 4 of 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.
authors: Department of Clinical Genetics, University Hospital, Lund, Sweden. anna.dahlen@klingen.lu.se
authors: Anna
authors: A
authors: Dahlén
authors: Fredrik
authors: F
authors: Mertens
authors: Anders
authors: A
authors: Rydholm
authors: Otte
authors: O
authors: Brosjö
authors: Johan
authors: J
authors: Wejde
authors: Nils
authors: N
authors: Mandahl
authors: Ioannis
authors: I
authors: Panagopoulos
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000595:Amino Acid Sequence; D001483:Base Sequence; D001859:Bone Neoplasms / Q000378:metabolism*; D002812:Chondroma / Q000378:metabolism*; D002813:Chondrosarcoma / Q000378:metabolism; D003598:Cytoskeletal Proteins / Q000235:genetics; D005260:Female; D015321:Gene Rearrangement; D025743:HMGA2 Protein / Q000235:genetics* / Q000378:metabolism*; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D060588:LIM Domain Proteins; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D011993:Recombinant Fusion Proteins / Q000378:metabolism*; D012983:Soft Tissue Neoplasms / Q000378:metabolism*
chemical_list: D003598:Cytoskeletal Proteins; D025743:HMGA2 Protein; D060588:LIM Domain Proteins; C103594:LPP protein, human; D011993:Recombinant Fusion Proteins