Identification of a gene expression driven progression pathway in myxoid liposarcoma.
Identification of a gene expression driven progression pathway in myxoid liposarcoma.
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DOI：
10.18632/oncotarget.2023
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发表时间：
2014-08-15
期刊：
影响因子：
--
通讯作者：
Pilotti S
中科院分区：
文献类型：
--
作者：
De Cecco L;Negri T;Brich S;Mauro V;Bozzi F;Dagrada G;Disciglio V;Sanfilippo R;Gronchi A;D'Incalci M;Casali PG;Canevari S;Pierotti MA;Pilotti S
目的：探讨黏液样脂肪肉瘤（MLS）发展过程中的相关事件。基因表达谱和免疫组织化学/生化分析应用于MLS谱的两端：纯黏液样（ML）和纯圆细胞（RC）脂肪肉瘤。分析显示编码和非编码rna（位于DLK1-DIO3区域的snord）都参与其中，并支持主要由涉及肿瘤血管供应和肿瘤细胞成分的表观遗传变化驱动的逐步进展模型。在该模型中，血管景观从正常到促血管生成特征的转换以及DLK1-DIO3区域的沉默标志着从ML到RC的进展，同时后者获得了YY1/C-MYC/HDAC2的过表达，以及参与细胞增殖和干细胞的基因：MKNK2， MSX1和TRIM71的过表达。综上所述，这些发现强烈表明，从ML到RC脂肪肉瘤的进展，细胞必须克服表观遗传沉默限制点，以重置其新的干细胞样分化特征。我们的研究结果为确定ML和RC脂肪肉瘤之间缺失的联系提供了首次尝试，这也可能在其他以进展谱为特征的临床病理环境中有更广泛的应用。
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 over-expression 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.
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DOI：
10.1038/nrg3473
发表时间：
2013-06
期刊：
Nature reviews. Genetics
影响因子：
--
作者：
通讯作者：
--
影响因子：
3.7
作者：
Hoshida Y;Brunet JP;Tamayo P;Golub TR;Mesirov JP
通讯作者：
Mesirov JP
影响因子：
20.1
作者：
Gorski, DH;Walsh, K
通讯作者：
Walsh, K
影响因子：
6.2
作者：
Hoffman, Aviad;Ghadimi, Markus P. H.;Pollock, Raphael E.
通讯作者：
Pollock, Raphael E.
影响因子：
11.8
作者：
Fish, Jason E.;Santoro, Massimo M.;Morton, Sarah U.;Yu, Sangho;Yeh, Ru-Fang;Wythe, Joshua D.;Lvey, Kathryn N.;Bruneau, Benoit G.;Stainier, Didier Y. R.;Srivastava, Deepak
通讯作者：
Srivastava, Deepak