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PMID: 19936258 Published · epublish English Journal Article Research Support, Non-U.S. Gov't

Epigenetic features of human mesenchymal stem cells determine their permissiveness for induction of relevant transcriptional changes by SYT-SSX1.

PloS one ·Vol. 4 ·No. 11 ·2009-11-19 ·Pages e7904

Cironi L, Provero P, Riggi N, Janiszewska M, Suva D, Suva ML, Kindler V, Stamenkovic I

Abstract

A characteristic SYT-SSX fusion gene resulting from the chromosomal translocation t(X;18)(p11;q11) is detectable in almost all synovial sarcomas, a malignant soft tissue tumor widely believed to originate from as yet unidentified pluripotent stem cells. The resulting fusion protein has no DNA binding motifs but possesses protein-protein interaction domains that are believed to mediate association with chromatin remodeling complexes. Despite recent advances in the identification of molecules that interact with SYT-SSX and with the corresponding wild type SYT and SSX proteins, the mechanisms whereby the SYT-SSX might contribute to neoplastic transformation remain unclear. Epigenetic deregulation has been suggested to be one possible mechanism. We addressed the effect of SYT/SSX expression on the transcriptome of four independent isolates of primary human bone marrow mesenchymal stem cells (hMSC). We observed transcriptional changes similar to the gene expression signature of synovial sarcoma, principally involving genes whose regulation is linked to epigenetic factors, including imprinted genes, genes with transcription start sites within a CpG island and chromatin related genes. Single population analysis revealed hMSC isolate-specific transcriptional changes involving genes that are important for biological functions of stem cells as well as genes that are considered to be molecular markers of synovial sarcoma including IGF2, EPHRINS, and BCL2. Methylation status analysis of sequences at the H19/IGF2 imprinted locus indicated that distinct epigenetic features characterize hMSC populations and condition the transcriptional effects of SYT-SSX expression. Our observations suggest that epigenetic features may define the cellular microenvironment in which SYT-SSX displays its functional effects.

MeSH Terms
Adolescent Alleles Child Chromatin/metabolism CpG Islands DNA/genetics Epigenesis, Genetic Gene Expression Profiling Gene Expression Regulation Humans Mesenchymal Stem Cells/cytology Oncogene Proteins, Fusion/genetics,physiology Sarcoma, Synovial/metabolism Transcription, Genetic Translocation, Genetic
Chemicals
Chromatin Oncogene Proteins, Fusion SYT-SSX fusion protein DNA
Authors & Affiliations
8 authors, click to expand affiliations / ORCID
Cironi Luisa
Division of Experimental Pathology, Institute of Pathology, Centre Hospitalier Universitaire Vaudois, Faculty of Biology and Medicine, University of Lausanne, Lausanne, Switzerland.
Provero Paolo
Riggi Nicola
Janiszewska Michalina
Suva Domizio
Suva Mario-Luca
Kindler Vincent
Stamenkovic Ivan
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Article Info
Journal
PloS one
Abbr.
PLoS One
ISSN
1932-6203
DOI
10.1371/journal.pone.0007904
Published
2009-11-19
Epub
2009-00-19
Pages
e7904
Language
English
Region
United States
NLM ID
101285081
PMCID
PMC2775947
Subset
IM
External Links
PubMed source DOI: 10.1371/journal.pone.0007904 PMC Full Text View journal details
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