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

Magdalena Koczkowska,Markku Miettinen,Mariola Iliszko,Wojciech Biernat,Beata Stefania Lipska-Ziętkiewicz,Anna Kruczak,Agnieszka Harazin-Lechowska,Jerzy Lasota,Janusz Ryś,Janusz Limon

doi:10.1186/s13039-017-0309-5

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.

Highlights

Rarity and heterogeneity of liposarcomas (LPS) make their diagnosis difficult even for sarcoma-experts pathologists
Liposarcomas are divided into four main subtypes: well-differentiated (WDLPS), dedifferentiated (DDLPS), myxoid/round cell (MLPS/MRLPS) and pleomorphic liposarcomas (PLPS)
Tumor specimens In total, 69 fresh-frozen tissue samples from 53 patients diagnosed with liposarcomas were included in this study: 23 WDLPS, 23 DDLPS and 23 MLPS

Summary

Introduction

Rarity and heterogeneity of liposarcomas (LPS) make their diagnosis difficult even for sarcoma-experts pathologists. CNAs in LPS were mostly evaluated using classical cytogenetic and targeted FISH approaches It allowed identification of supernumerary ring giant chromosomes and double-minute chromosomes (dmin) in WDLPS and DDLS. MLPS, the third subtype of LPS, is distinguished by the presence of a specific translocation t(12;16) [7] or t(12;22) [8] that is the key genetic aberration, extremely helpful in differential diagnosis between MLPS and myxofibrosarcomas [5] These unique chromosomal translocations, detected in more than 95% of cases, result from a fusion of the segments of the DDIT3 gene (12q13) and the FUS gene (16p11) or the EWSR1 gene (22q12) [1, 9]

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