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Characterization of the 12q amplicons by high-resolution, oligonucleotide array CGH and expression analyses of a novel liposarcoma cell line

Journal article
Authors Fredrik Persson
Anita Olofsson
Helene Sjögren
Nihal Chebbo
Bengt E Nilsson
Göran Stenman
Pierre Åman
Published in Cancer Letters
Volume 260
Issue 1-2
Pages 37-47
ISSN 0304-3835
Publication year 2008
Published at Institute of Clinical Sciences, Department of Surgery
Institute of Biomedicine, Department of Pathology
Pages 37-47
Language en
Links dx.doi.org/10.1016/j.canlet.2007.10...
Keywords Aged, Cell Cycle Proteins/genetics, Cell Differentiation, Cell Line, Tumor, Chromosomes, Human, Pair 1, *Chromosomes, Human, Pair 12, Chromosomes, Human, Pair 13, Cytogenetic Analysis, Female, *Gene Amplification, Gene Expression Profiling/*methods, *Gene Expression Regulation, Neoplastic, Gene Rearrangement, Humans, Liposarcoma/*genetics/pathology, *Oligonucleotide Array Sequence Analysis, Retroperitoneal Neoplasms/*genetics/pathology, Spectral Karyotyping
Subject categories Pathology

Abstract

The cytogenetic hallmark of well-differentiated liposarcoma (WDLS) is a giant marker chromosomes containing amplified genes from chromosome 12q13-q15. Here, we have employed SKY and high-resolution 244K oligonucleotide array CGH to characterize rearrangements and amplifications in a new WDLS cell line (GOT3) with a giant marker chromosome derived from chromosomes 12, 1, and X. The most prominent amplifications included 144 genes in 12q11-q21.2, 201 genes in 1q23.3-q44, and six genes in 13q32.1-q32.2. In the 12q amplicons, MDM2 showed the highest level of amplification followed by LYZ, HMGA2 (5'-part), TSPAN8, CNOT2, YEATS4, CDK4, GNS, HELB, and TSFM. Expression analysis of genes from the three major amplicons revealed that several highly amplified potential target genes, including HMGA2, MDM2, YEATS4, CDK4, PKP1, IPO9, and SOX21, were strongly overexpressed. Studies of cell cycle controlling proteins that interact with CDK4 and MDM2 revealed an abnormally strong expression of cyclins D1 and E. The selective high-level amplification of the 5'-part of HMGA2, including the DNA-binding domains, suggests that this gene is a major target of amplifications in WDLS. Our results also identify several novel candidate genes of potential pathogenetic and therapeutic importance for WDLS.

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