title: Characterization of the 12q amplicons in lipomatous soft tissue tumors by multiplex ligation-dependent probe amplification-based copy number analysis.
abstract: OBJECTIVE
  Well-differentiated liposarcoma (WDLPS) and de-differentiated liposarcoma (DDLPS) are characterized by amplified sequences derived from the long arm of chromosome 12. The goal of the present study was to identify, besides the well-known candidate genes, novel relevant genes in these large, complex 12q amplicons.
  
  
  METHODS
  Using multiplex ligation-dependent probe amplification, genetic alterations in 19 different genes of 12q12-24 were evaluated in 77 lipomatous soft tissue tumors (including lipomas, WDLPS, DDLPS and pleomorphic liposarcomas).
  
  
  RESULTS
  We recorded several amplified genes of 12q13-15, including miR-26a-2, a gene not well studied in liposarcoma, and the well-known and previously described genes murine double minute 2 (MDM2), YEATS domain-containing protein 4 (YEATS4), high-mobility AT-hook 2 (HMGA2), cyclin-dependent kinase 4 (CDK4) and tetraspanin 31 (TSPAN31). Interestingly, the amplification profiles of these six genes were found to be significantly different between WDLPS and DDLPS, more frequently having a high-level status in DDLPS than in WDLPS. In addition, DDLPS were found to have significantly higher mean amplification ratios compared to WDLPS. Moreover, we identified additional genes exclusively amplified in DDLPS in 12q13, 12q21 and 12q24, including glioma-associated oncogene homolog 1 (GLI1), mitogen activated protein kinase kinase kinase 12 (MAP3K12), cyclin-dependent kinase 2 (CDK2), ALX homeobox 1 (ALX1) and T-box 5 (TBX5).
  
  
  CONCLUSIONS
  Differences in amplification profiles among WDLPS and DDLPS may be related to progression/de-differentiation in liposarcomas and show how in the future amplification profiles could provide an adjunctive tool in characterizing progression to DDLPS. In addition, we identified additional genes exclusively amplified in DDLPS, which may play a role in liposarcomagenesis, particularly in the de-differentiation process.
authors: Department of Pathology, Ghent University and Ghent University Hospital, Ghent, Belgium david.creytens@uzgent.be creytensdavid@hotmail.com.
authors: David
authors: D
authors: Creytens
authors: Department of Pathology, Diakonessenhuis Hospital Utrecht, Utrecht, the Netherlands.
authors: Joost
authors: J
authors: Van Gorp
authors: Department of Pathology, GROW-School for Oncology and Developmental Biology, Maastricht University Medical Center, Maastricht, the Netherlands.
authors: Ernst-Jan
authors: EJ
authors: Speel
authors: Department of Pathology, Ghent University and Ghent University Hospital, Ghent, Belgium.
authors: Liesbeth
authors: L
authors: Ferdinande
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D002454:Cell Differentiation / Q000235:genetics; D002881:Chromosomes, Human, Pair 12 / Q000235:genetics; D056915:DNA Copy Number Variations / Q000235:genetics*; D005260:Female; D005784:Gene Amplification / Q000235:genetics; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008067:Lipoma / Q000235:genetics* / Q000473:pathology; D008080:Liposarcoma / Q000235:genetics* / Q000473:pathology; D008297:Male; D051379:Mice; D008875:Middle Aged; D060885:Multiplex Polymerase Chain Reaction; D009363:Neoplasm Proteins / Q000235:genetics*; D012983:Soft Tissue Neoplasms / Q000235:genetics* / Q000473:pathology
chemical_list: D009363:Neoplasm Proteins
keywords: 12q amplicon; Lipoma; dedifferentiated liposarcoma; multiplex ligation-dependent probe amplification; pleomorphic liposarcoma; well-differentiated liposarcoma