Identification of PPAP2B as a novel recurrent translocation partner gene of HMGA2 in lipomas. Issue 6 (18th March 2013)

• Record Type: Journal Article
• Authors: Bianchini, Laurence; Birtwisle, Loïc; Saâda, Esma; Bazin, Audrey; Long, Elodie; Roussel, Jean‐François; Michiels, Jean‐François; Forest, Fabien; Dani, Christian; Myklebost, Ola; Birtwisle‐Peyrottes, Isabelle; Pedeutour, Florence
• Is Part Of: Genes, chromosomes & cancer. Volume 52:Issue 6(2013:Jun.)
• Page Start: 580
• Page End: 590
• Publication Date: 2013-03-18
• Subjects: Cancer -- Genetic aspects -- Periodicals; 616.994042
• DOI: 10.1002/gcc.22055
• Languages: English
• ISSNs: 1045-2257

Abstract

<abstract abstract-type="main" xml:lang="en"> <title>Abstract</title> <p>Most lipomas are characterized by translocations involving the <italic>HMGA2</italic> gene in 12q14.3. These rearrangements lead to the fusion of <italic>HMGA2</italic> with an ectopic sequence from the translocation chromosome partner. Only five fusion partners of <italic>HMGA2</italic> have been identified in lipomas so far. The identification of novel fusion partners of <italic>HMGA2</italic> is important not only for diagnosis in soft tissue tumors but also because these genes might have an oncogenic role in other tumors. We observed that t(1;12)(p32;q14) was the second most frequent translocation in our series of lipomas after t(3;12)(q28;q14.3). We detected overexpression of <italic>HMGA2</italic> mRNA and protein in all t(1;12)(p32;q14) lipomas. We used a fluorescence in situ hybridization‐based positional cloning strategy to characterize the 1p32 breakpoint. In 11 cases, we identified <italic>PPAP2B</italic>, a member of the lipid phosphate phosphatases family as the 1p32 target gene. Reverse transcription‐polymerase chain reaction analysis followed by nucleotide sequencing of the fusion transcript indicated that <italic>HMGA2</italic> 3′ untranslated region (3′UTR) fused with exon 6 of <italic>PPAP2B</italic> in one case. In other t(1;12) cases, the breakpoint was extragenic, located in the 3′region flanking <italic>PPAP2B</italic> 3′UTR. Moreover, in one case showing a t(1;6)(p32;p21) we observed a rearrangement of <italic>PPAP2B</italic> and <italic>HMGA1</italic>, which suggests that <italic>HMGA1</italic> might also be a fusion partner for <italic>PPAP2B</italic>. Our results also revealed that adipocytic differentiation of human mesenchymal stem cells derived from adipose tissue was associated with a significant decrease in <italic>PPAP2B</italic> mRNA expression suggesting that <italic>PPAP2B</italic> might play a role in adipogenesis. © 2013 Wiley Periodicals, Inc.</p> </abstract>