David Creytens1, Joost Van Gorp2, Ernst-Jan Speel3, Liesbeth Ferdinande4. 1. Department of Pathology, Ghent University and Ghent University Hospital, Ghent, Belgium david.creytens@uzgent.be creytensdavid@hotmail.com. 2. Department of Pathology, Diakonessenhuis Hospital Utrecht, Utrecht, the Netherlands. 3. Department of Pathology, GROW-School for Oncology and Developmental Biology, Maastricht University Medical Center, Maastricht, the Netherlands. 4. Department of Pathology, Ghent University and Ghent University Hospital, Ghent, Belgium.
Abstract
BACKGROUND/AIM: 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. MATERIALS AND 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). CONCLUSION: 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. Copyright
BACKGROUND/AIM: 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. MATERIALS AND 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). CONCLUSION: 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. Copyright