TY - JOUR
T1 - Identification of a gene expression driven progression pathway in Myxoid liposarcoma
AU - De Cecco, Loris D.
AU - Negri, Tiziana
AU - Brich, Silvia
AU - Mauro, Valentina
AU - Bozzi, Fabio
AU - Dagrada, GianPaolo
AU - Disciglio, Vittoria
AU - Sanfilippo, Roberta
AU - Gronchi, Alessandro
AU - Maurizio D'Incalci, D'Incalci
AU - Casali, Paolo G.
AU - Canevari, Silvana
AU - Pierotti, Marco A.
AU - Pilotti, Silvana
PY - 2014
Y1 - 2014
N2 - 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.
AB - 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.
KW - Epigenetic deregulation
KW - Fast cell cycle related genes
KW - Gene expression array
KW - Myxoid liposarcoma
KW - Progression to round cell
KW - Stemness related genes
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M3 - Article
C2 - 25115389
AN - SCOPUS:84906251746
VL - 5
SP - 5965
EP - 5977
JO - Oncotarget
JF - Oncotarget
SN - 1949-2553
IS - 15
ER -