title: The recurrent chromosomal translocation t(12;18)(q14~15;q12~21) causes the fusion gene HMGA2-SETBP1 and HMGA2 expression in lipoma and osteochondrolipoma.
abstract: Lipomas are the most common soft tissue tumors in adults. They often carry chromosome aberrations involving 12q13~15 leading to rearrangements of the HMGA2 gene in 12q14.3, with breakpoints occurring within or outside of the gene. Here, we present eleven lipomas and one osteochondrolipoma with a novel recurrent chromosome aberration, t(12;18)(q14~15;q12~21). Molecular studies on eight of the tumors showed that full-length HMGA2 transcript was expressed in three and a chimeric HMGA2 transcript in five of them. In three lipomas and in the osteochondrolipoma, exons 1-3 of HMGA2 were fused to a sequence of SETBP1 on 18q12.3 or an intragenic sequence from 18q12.3 circa 10 kbp distal to SETBP1. In another lipoma, exons 1-4 of HMGA2 were fused to an intronic sequence of GRIP1 which maps to chromosome band 12q14.3, distal to HMGA2. The ensuing HMGA2 fusion transcripts code for putative proteins which contain amino acid residues of HMGA2 corresponding to exons 1-3 (or exons 1-4 in one case) followed by amino acid residues corresponding to the fused sequences. Thus, the pattern is similar to the rearrangements of HMGA2 found in other lipomas, i.e., disruption of the HMGA2 locus leaves intact exons 1-3 which encode the AT-hooks domains and separates them from the 3'-terminal part of the gene. The fact that the examined osteochondrolipoma had a t(12;18) and a HMGA2-SETBP1 fusion identical to the findings in the much more common ordinary lipomas, underscores the close developmental relationship between the two tumor types.
authors.affiliation: Section for Cancer Cytogenetics, Institute for Cancer Genetics and Informatics, The Norwegian Radium Hospital, Oslo University Hospital, Oslo, Norway.
authors.forename: Ioannis
authors.initials: I
authors.lastname: Panagopoulos
authors.affiliation: Section for Cancer Cytogenetics, Institute for Cancer Genetics and Informatics, The Norwegian Radium Hospital, Oslo University Hospital, Oslo, Norway.
authors.forename: Ludmila
authors.initials: L
authors.lastname: Gorunova
authors.affiliation: Department of Pathology, The Norwegian Radium Hospital, Oslo University Hospital, Oslo, Norway.
authors.forename: Bodil
authors.initials: B
authors.lastname: Bjerkehagen
authors.affiliation: Department of Pathology, The Norwegian Radium Hospital, Oslo University Hospital, Oslo, Norway.
authors.forename: Ingvild
authors.initials: I
authors.lastname: Lobmaier
authors.affiliation: Section for Cancer Cytogenetics, Institute for Cancer Genetics and Informatics, The Norwegian Radium Hospital, Oslo University Hospital, Oslo, Norway.
authors.forename: Sverre
authors.initials: S
authors.lastname: Heim
mesh_terms: D000328:Adult; D001842:Bone and Bones / Q000473:pathology*; D002352:Carrier Proteins / Q000235:genetics*; D002356:Cartilage / Q000473:pathology*; D002881:Chromosomes, Human, Pair 12 / Q000235:genetics; D002887:Chromosomes, Human, Pair 18 / Q000235:genetics; D005260:Female; D025743:HMGA2 Protein / Q000235:genetics*; D006801:Humans; D008067:Lipoma / Q000235:genetics* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009687:Nuclear Proteins / Q000235:genetics*; D015514:Oncogene Proteins, Fusion / Q000235:genetics; D014178:Translocation, Genetic
chemical_list: D002352:Carrier Proteins; D025743:HMGA2 Protein; D009687:Nuclear Proteins; D015514:Oncogene Proteins, Fusion; C425066:SETBP1 protein, human