Identification of a gene expression driven progression pathway in Myxoid liposarcoma

Loris D. De Cecco, Tiziana Negri, Silvia Brich, Valentina Mauro, Fabio Bozzi, GianPaolo Dagrada, Vittoria Disciglio, Roberta Sanfilippo, Alessandro Gronchi, D'Incalci Maurizio D'Incalci, Paolo G. Casali, Silvana Canevari, Marco A. Pierotti, Silvana Pilotti

Research output: Contribution to journalArticlepeer-review

Abstract

Aim: to investigate the events involved in the progression of myxoid liposarcoma (MLS). Gene expression profiling and immunohistochemical/biochemical analyses were applied to specimens representative of the opposite ends of the MLS spectrum: pure myxoid (ML) and pure round cell (RC) liposarcomas. The analyses revealed the involvement of both coding and non coding RNAs (SNORDs located in DLK1-DIO3 region) and support a model of stepwise progression mainly driven by epigenetic changes involving tumour vascular supply and tumoral cellular component. In this model, a switch in the vascular landscape from a normal to a pro-angiogenic signature and the silencing of DLK1-DIO3 region mark the progression from ML to RC in concert with the acquisition by the latter of the overexpression of YY1/C-MYC/HDAC2, together with over-expression of genes involved in cell proliferation and stemness: MKNK2, MSX1 and TRIM71. Taken together, these findings strongly suggest that to progress from ML to RC liposarcoma the cells have to overcome the epigenetic silencing restriction point in order to reset their new stem-like differentiation signature. Our findings provide a first attempt at identifying the missing links between ML and RC liposarcomas, that may also have broader applications in other clinico-pathological settings characterised by a spectrum of progression.

Original languageEnglish
Pages (from-to)5965-5977
Number of pages13
JournalOncotarget
Volume5
Issue number15
Publication statusPublished - 2014

Keywords

  • Epigenetic deregulation
  • Fast cell cycle related genes
  • Gene expression array
  • Myxoid liposarcoma
  • Progression to round cell
  • Stemness related genes

ASJC Scopus subject areas

  • Oncology
  • Medicine(all)

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