Application of high-resolution genomic profiling in the differential diagnosis of liposarcoma

Abstract

BackgroundRarity and heterogeneity of liposarcomas (LPS) make their diagnosis difficult even for sarcoma-experts pathologists. The molecular mechanism underlying the development and progression of liposarcomas (LPS) remains only partially known. In order to identify and compare the genomic profiles, we analyzed array-based comparative genomic hybridization (array-CGH) profiles of 66 liposarcomas, including well-differentiated (WDLPS), dedifferentiated (DDLPS) and myxoid (MLPS) subtypes.ResultsCopy number aberrations (CNAs) were identified in 98% of WDLPS and DDLPS and in 95% of MLPS cases. The minimal common region of amplification at 12q14.1q21.1 was observed in 96% of WDLPS and DDLPS cases. Four regions of CNAs, including losses of chromosome 6, 11 and 13 and gains of chromosome 14 were classified as recurrent in DDLPS; at least one was identified in 74% of DDLPS tumors. The DDLPS-associated losses were much more common in tumors with increased genomic complexity. In MLPS, the most frequent CNAs were losses of chromosome 6 (40%) and gains of chromosome 1 (30%), with the minimal overlapping regions 6q14.1q22.31 and 1q25.1q32.2, respectively.ConclusionsOur findings show that the application of array-CGH allows to delineate clearly the genomic profiles of WDLPS, DDLPS and MLPS that reflect biological differences between these tumors. Although CNAs varied widely, the subtypes of tumors have characteristic genomic profiles that could facilitate the differential diagnosis of LPS subtypes, especially between WDLPS and DDLPS.Electronic supplementary materialThe online version of this article (doi:10.1186/s13039-017-0309-5) contains supplementary material, which is available to authorized users.

Cytogenomic Characterization of Giant Ring or Rod Marker Chromosome in Four Cases of Well-Differentiated and Dedifferentiated Liposarcoma

“…These patterns supported the MDM2 as the main driver gene and other genes as codriver or passenger genes. The SCNAs in other chromosomes including amplifications of 1p32.2 (JUN), 12q13.3(GLI1), 6q23.3 (MAP3K5), losses of 6p, 6q, 11p, 11q, and 13q, and gains of 14q have been reported to be associated with DDLPS [ 10 , 13 , 15 ]. However, these SCNAs were not observed in the present three cases.…”

Clinical Application of Chromosome Microarray Analysis in the Diagnosis of Lipomatous Tumors

“…ALT/WDLS and DDLS are characterized by the amplification of sequences of the 12q13-15 chromosome region containing MDM2 (12q15), CDK4 (12q14.1), HMGA2 (12q14.3), YEATS4 (12q15), CPM (12q15), and FRS2 (12q15). [8][9][10][11][12][13][14]18 MDM2 protein bonds p53 protein to form a complex that can inhibit the p53 growth suppressive function by blocking the transactivation domain of p53. CDK4 phosphorylates RB1 and is implicated in the G1-S checkpoint of the cell cycle.…”

Comprehensive Bioinformatic Analysis Genes Associated to the Prognosis of Liposarcoma

“…In addition, there is an imperative need for prognostic factors that can reliable pinpoint the outcomes in patients with liposarcoma [ 13 ]. Recently, several genomic analyses studies reported a molecular catalogue that significant related to the liposarcoma tumorigenesis and outcome [ 14 – 17 ]. Tap et al [ 18 ] identified chromosomal and genetic abnormalities in well-differentiated and de-differentiated liposarcoma using an oligonucleotide array-based comparative genomic hybridization approach.…”