title: Expression levels of HMGA2 in adipocytic tumors correlate with morphologic and cytogenetic subgroups.
abstract: BACKGROUND
  The HMGA2 gene encodes a protein that alters chromatin structure. Deregulation, typically through chromosomal rearrangements, of HMGA2 has an important role in the development of several mesenchymal neoplasms. These rearrangements result in the expression of a truncated protein lacking the acidic C-terminus, a fusion protein consisting of the AT-hook domains encoded by exons 1-3 and parts from another gene, or a full-length protein; loss of binding sites for regulatory microRNA molecules from the 3' untranslated region (UTR) of HMGA2 has been suggested to be a common denominator.
  
  
  METHODS
  Seventy adipocytic tumors, representing different morphologic and cytogenetic subgroups, were analyzed by qRT-PCR to study the expression status of HMGA2; 18 of these tumors were further examined by PCR to search for mutations or deletions in the 3'UTR.
  
  
  RESULTS
  Type (full-length or truncated) and level of expression varied with morphology and karyotype, with the highest levels in atypical lipomatous tumors and lipomas with rearrangements of 12q13-15 and the lowest in lipomas with 6p- or 13q-rearrangements, hibernomas, spindle cell lipomas and myxoid liposarcomas. All 18 examined tumors showed reduced or absent expression of the entire, or parts of, the 3'UTR, which was not due to mutations at the DNA level.
  
  
  CONCLUSIONS
  In adipocytic tumors with deregulated HMGA2 expression, the 3'UTR is consistently lost, either due to physical disruption of HMGA2 or a shift to production of shorter 3'UTR.
authors.affiliation: Department of Clinical Genetics, Lund University Hospital, Lund, Sweden. hammurabi.bartuma@med.lu.se
authors.forename: Hammurabi
authors.initials: H
authors.lastname: Bartuma
authors.forename: Ioannis
authors.initials: I
authors.lastname: Panagopoulos
authors.forename: Anna
authors.initials: A
authors.lastname: Collin
authors.forename: Domenico
authors.initials: D
authors.lastname: Trombetta
authors.forename: Henryk A
authors.initials: HA
authors.lastname: Domanski
authors.forename: Nils
authors.initials: N
authors.lastname: Mandahl
authors.forename: Fredrik
authors.initials: F
authors.lastname: Mertens
mesh_terms: D020413:3' Untranslated Regions / Q000235:genetics; D020732:Cytogenetic Analysis; D020869:Gene Expression Profiling / Q000379:methods*; D015321:Gene Rearrangement; D025743:HMGA2 Protein / Q000235:genetics* / Q000378:metabolism*; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008067:Lipoma / Q000145:classification / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D008677:Metaphase; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017422:Sequence Analysis, DNA
chemical_list: D020413:3' Untranslated Regions; D025743:HMGA2 Protein