title: Identification of a gene expression driven progression pathway in myxoid liposarcoma.
abstract: 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 over-expression of YYI/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.
authors.affiliation: Functional Genomics and Bioinformatics, Department of Experimental Oncology and Molecular Medicine, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan Italy; These authors contributed equally to this work.
authors.forename: Loris
authors.initials: L
authors.lastname: De Cecco
authors.affiliation: Laboratory of Experimental Molecular Pathology, Department of Diagnostic Pathology and Laboratory, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan Italy; These authors contributed equally to this work.
authors.forename: Tiziana
authors.initials: T
authors.lastname: Negri
authors.affiliation: Laboratory of Experimental Molecular Pathology, Department of Diagnostic Pathology and Laboratory, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan Italy.
authors.forename: Silvia
authors.initials: S
authors.lastname: Brich
authors.affiliation: Laboratory of Experimental Molecular Pathology, Department of Diagnostic Pathology and Laboratory, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan Italy.
authors.forename: Valentina
authors.initials: V
authors.lastname: Mauro
authors.affiliation: Laboratory of Experimental Molecular Pathology, Department of Diagnostic Pathology and Laboratory, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan Italy.
authors.forename: Fabio
authors.initials: F
authors.lastname: Bozzi
authors.affiliation: Laboratory of Experimental Molecular Pathology, Department of Diagnostic Pathology and Laboratory, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan Italy.
authors.forename: GianPaolo
authors.initials: G
authors.lastname: Dagrada
authors.affiliation: Functional Genomics and Bioinformatics, Department of Experimental Oncology and Molecular Medicine, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan Italy.
authors.forename: Vittoria
authors.initials: V
authors.lastname: Disciglio
authors.affiliation: Adult Mesenchymal Tumor Medical Oncology Unit, Cancer Medicine Department, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan Italy.
authors.forename: Roberta
authors.initials: R
authors.lastname: Sanfilippo
authors.affiliation: Department of Surgery, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan Italy.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Gronchi
authors.affiliation: Department of Oncology, IRCCS, Istituto di Ricerche Farmacologiche Mario Negri, Milan, Italy.
authors.forename: Maurizio
authors.initials: M
authors.lastname: D'Incalci
authors.affiliation: Adult Mesenchymal Tumor Medical Oncology Unit, Cancer Medicine Department, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan Italy.
authors.forename: Paolo G
authors.initials: PG
authors.lastname: Casali
authors.affiliation: Functional Genomics and Bioinformatics, Department of Experimental Oncology and Molecular Medicine, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan Italy.
authors.forename: Silvana
authors.initials: S
authors.lastname: Canevari
authors.affiliation: Scientific Directorate, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan Italy.
authors.forename: Marco A
authors.initials: MA
authors.lastname: Pierotti
authors.affiliation: Laboratory of Experimental Molecular Pathology, Department of Diagnostic Pathology and Laboratory, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan Italy.
authors.forename: Silvana
authors.initials: S
authors.lastname: Pilotti
mesh_terms: D018450:Disease Progression; D057890:Epigenomics / Q000379:methods; D015870:Gene Expression; D020869:Gene Expression Profiling; D006801:Humans; D018208:Liposarcoma, Myxoid / Q000235:genetics* / Q000378:metabolism / Q000473:pathology