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FUS-CREB3L2/L1-Positive Sarcomas Show a Specific Gene Expression Profile with Upregulation of CD24 and FOXL1.

Möller, Emely LU ; Hornick, Jason L; Magnusson, Linda LU ; Veerla, Srinivas; Domanski, Henryk LU and Mertens, Fredrik LU (2011) In Clinical Cancer Research 17(9). p.2646-2656
Abstract
Abstract

PURPOSE:

Low-grade fibromyxoid sarcoma (LGFMS) is typically characterized by the specific translocation t(7;16)(q33;p11) and the corresponding fusion gene FUS-CREB3L2. The present study aimed to extract LGFMS-specific, and putatively FUS-CREB3L2-dependent, gene expression patterns to learn more about the pathogenesis of this tumor.



EXPERIMENTAL DESIGN:

We carried out single nucleotide polymorphism (SNP) and global gene expression array analyses, and/or immunohistochemical (IHC) analyses on 24 LGFMS tumor biopsies. Tumor types that are important differential diagnoses to LGFMS were included as comparison in the gene and protein expression analyses. In addition, cells that stably... (More)
Abstract

PURPOSE:

Low-grade fibromyxoid sarcoma (LGFMS) is typically characterized by the specific translocation t(7;16)(q33;p11) and the corresponding fusion gene FUS-CREB3L2. The present study aimed to extract LGFMS-specific, and putatively FUS-CREB3L2-dependent, gene expression patterns to learn more about the pathogenesis of this tumor.



EXPERIMENTAL DESIGN:

We carried out single nucleotide polymorphism (SNP) and global gene expression array analyses, and/or immunohistochemical (IHC) analyses on 24 LGFMS tumor biopsies. Tumor types that are important differential diagnoses to LGFMS were included as comparison in the gene and protein expression analyses. In addition, cells that stably expressed FUS-CREB3L2 were analyzed with gene expression array and the influence of FUS-CREB3L2 on gene expression was investigated in vitro.



RESULTS:

The SNP array analysis detected recurrent microdeletions in association with the t(7;16) chromosomal breakpoints and gain of 7q in cases with ring chromosomes. Gene expression analysis clearly distinguished LGFMS from morphologically similar tumors and MUC4 was identified as a potential diagnostic marker for LGFMS by gene expression and IHC analysis. FOXL1 was identified as the top upregulated gene in LGFMS and CD24 was upregulated in both LGFMS tumors and FUS-CREB3L2 expressing cells. FUS-CREB3L2 was capable of activating transcription from CD24 regulatory sequences in luciferase assays, suggesting an important role for the upregulation of this gene in LGFMS.



CONCLUSIONS:

The gene expression profile of LGFMS is distinct from that of soft tissue tumors with similar morphology. The data could be used to identify a potential diagnostic marker for LGFMS and to identify possible FUS-CREB3L2 regulated genes. Clin Cancer Res; 17(9); 2646-56. ©2011 AACR. (Less)
Please use this url to cite or link to this publication:
author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Clinical Cancer Research
volume
17
issue
9
pages
2646 - 2656
publisher
American Association for Cancer Research
external identifiers
  • wos:000290093600007
  • pmid:21536545
  • scopus:79955502348
ISSN
1078-0432
DOI
10.1158/1078-0432.CCR-11-0145
language
English
LU publication?
yes
id
65c223de-0818-4f93-bfb0-5e1469c68243 (old id 1973214)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/21536545?dopt=Abstract
date added to LUP
2011-06-07 10:50:09
date last changed
2017-08-13 04:34:01
@article{65c223de-0818-4f93-bfb0-5e1469c68243,
  abstract     = {Abstract<br/><br>
PURPOSE:<br/><br>
Low-grade fibromyxoid sarcoma (LGFMS) is typically characterized by the specific translocation t(7;16)(q33;p11) and the corresponding fusion gene FUS-CREB3L2. The present study aimed to extract LGFMS-specific, and putatively FUS-CREB3L2-dependent, gene expression patterns to learn more about the pathogenesis of this tumor.<br/><br>
<br/><br>
EXPERIMENTAL DESIGN:<br/><br>
We carried out single nucleotide polymorphism (SNP) and global gene expression array analyses, and/or immunohistochemical (IHC) analyses on 24 LGFMS tumor biopsies. Tumor types that are important differential diagnoses to LGFMS were included as comparison in the gene and protein expression analyses. In addition, cells that stably expressed FUS-CREB3L2 were analyzed with gene expression array and the influence of FUS-CREB3L2 on gene expression was investigated in vitro.<br/><br>
<br/><br>
RESULTS:<br/><br>
The SNP array analysis detected recurrent microdeletions in association with the t(7;16) chromosomal breakpoints and gain of 7q in cases with ring chromosomes. Gene expression analysis clearly distinguished LGFMS from morphologically similar tumors and MUC4 was identified as a potential diagnostic marker for LGFMS by gene expression and IHC analysis. FOXL1 was identified as the top upregulated gene in LGFMS and CD24 was upregulated in both LGFMS tumors and FUS-CREB3L2 expressing cells. FUS-CREB3L2 was capable of activating transcription from CD24 regulatory sequences in luciferase assays, suggesting an important role for the upregulation of this gene in LGFMS.<br/><br>
<br/><br>
CONCLUSIONS:<br/><br>
The gene expression profile of LGFMS is distinct from that of soft tissue tumors with similar morphology. The data could be used to identify a potential diagnostic marker for LGFMS and to identify possible FUS-CREB3L2 regulated genes. Clin Cancer Res; 17(9); 2646-56. ©2011 AACR.},
  author       = {Möller, Emely and Hornick, Jason L and Magnusson, Linda and Veerla, Srinivas and Domanski, Henryk and Mertens, Fredrik},
  issn         = {1078-0432},
  language     = {eng},
  number       = {9},
  pages        = {2646--2656},
  publisher    = {American Association for Cancer Research},
  series       = {Clinical Cancer Research},
  title        = {FUS-CREB3L2/L1-Positive Sarcomas Show a Specific Gene Expression Profile with Upregulation of CD24 and FOXL1.},
  url          = {http://dx.doi.org/10.1158/1078-0432.CCR-11-0145},
  volume       = {17},
  year         = {2011},
}