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Aberrant epigenetic regulation in clear cell sarcoma of the kidney featuring distinct DNA hypermethylation and EZH2 overexpression.

Karlsson, Jenny LU ; Valind, Anders LU ; Jansson, Caroline LU ; O'Sullivan, Maureen J; Holmquist Mengelbier, Linda LU and Gisselsson Nord, David LU (2016) In Oncotarget 7(10). p.36-11127
Abstract
The global methylation profile and the mutational status of 633 specific epigenetic regulators were analyzed in the pediatric tumor clear cell sarcoma of the kidney (CCSK). Methylation array analyses of 30 CCSKs revealed CCSK tumor DNA to be globally hypermethylated compared to Wilms tumor, normal fetal kidney, and adult kidney. The aberrant methylation pattern of CCSKs was associated with activation of genes involved in embryonic processes and with silencing of genes linked to normal kidney function. No epigenetic regulator was recurrently mutated in our cohort, but a mutation in the key epigenetic regulator EZH2 was discovered in one case. EZH2 mRNA was significantly higher in CCSK compared to Wilms tumor and normal kidney, and the EZH2... (More)
The global methylation profile and the mutational status of 633 specific epigenetic regulators were analyzed in the pediatric tumor clear cell sarcoma of the kidney (CCSK). Methylation array analyses of 30 CCSKs revealed CCSK tumor DNA to be globally hypermethylated compared to Wilms tumor, normal fetal kidney, and adult kidney. The aberrant methylation pattern of CCSKs was associated with activation of genes involved in embryonic processes and with silencing of genes linked to normal kidney function. No epigenetic regulator was recurrently mutated in our cohort, but a mutation in the key epigenetic regulator EZH2 was discovered in one case. EZH2 mRNA was significantly higher in CCSK compared to Wilms tumor and normal kidney, and the EZH2 protein was strongly expressed in more than 90 % of CCSK tumor cells in 9/9 tumors analyzed. This was in striking contrast to the lack of EZH2 protein expression in Wilms tumor stromal elements, indicating that EZH2 could be explored further as a diagnostic marker and a potential drug target for CCSK. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Oncotarget
volume
7
issue
10
pages
36 - 11127
publisher
Impact Journals, LLC
external identifiers
  • PMID:26848979
  • Scopus:84962027625
ISSN
1949-2553
DOI
10.18632/oncotarget.7152
language
English
LU publication?
yes
id
a1cb5dd6-8072-4cc5-acd7-fd38d5dc523c (old id 8829195)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/26848979?dopt=Abstract
date added to LUP
2016-03-01 13:48:36
date last changed
2016-10-13 04:33:16
@misc{a1cb5dd6-8072-4cc5-acd7-fd38d5dc523c,
  abstract     = {The global methylation profile and the mutational status of 633 specific epigenetic regulators were analyzed in the pediatric tumor clear cell sarcoma of the kidney (CCSK). Methylation array analyses of 30 CCSKs revealed CCSK tumor DNA to be globally hypermethylated compared to Wilms tumor, normal fetal kidney, and adult kidney. The aberrant methylation pattern of CCSKs was associated with activation of genes involved in embryonic processes and with silencing of genes linked to normal kidney function. No epigenetic regulator was recurrently mutated in our cohort, but a mutation in the key epigenetic regulator EZH2 was discovered in one case. EZH2 mRNA was significantly higher in CCSK compared to Wilms tumor and normal kidney, and the EZH2 protein was strongly expressed in more than 90 % of CCSK tumor cells in 9/9 tumors analyzed. This was in striking contrast to the lack of EZH2 protein expression in Wilms tumor stromal elements, indicating that EZH2 could be explored further as a diagnostic marker and a potential drug target for CCSK.},
  author       = {Karlsson, Jenny and Valind, Anders and Jansson, Caroline and O'Sullivan, Maureen J and Holmquist Mengelbier, Linda and Gisselsson Nord, David},
  issn         = {1949-2553},
  language     = {eng},
  number       = {10},
  pages        = {36--11127},
  publisher    = {ARRAY(0xb62b0b8)},
  series       = {Oncotarget},
  title        = {Aberrant epigenetic regulation in clear cell sarcoma of the kidney featuring distinct DNA hypermethylation and EZH2 overexpression.},
  url          = {http://dx.doi.org/10.18632/oncotarget.7152},
  volume       = {7},
  year         = {2016},
}