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Activation of human telomerase reverse transcriptase through gene fusion in clear cell sarcoma of the kidney.

Karlsson, Jenny LU ; Lilljebjörn, Henrik LU ; Holmquist Mengelbier, Linda LU ; Valind, Anders LU ; Rissler, Marianne LU ; Øra, Ingrid LU ; Fioretos, Thoas LU and Gisselsson Nord, David LU (2015) In Cancer Letters 357(2). p.498-501
Abstract
Clear cell sarcoma of the kidney (CCSK) is a rare tumor type affecting infants and young children. Most CCSKs display few genomic aberrations, and no general underlying mechanism for tumor initiation has yet been identified, although a YWHAE-NUTM2B/NUTM2E fusion gene has been observed in a minority of cases. We performed RNA-sequencing of 22 CCSKs to investigate the presence of additional fusion transcripts. The presence of the YWHAE-NUTM2B/NUTM2E fusion was confirmed in two cases. In addition, a novel IRX2-TERT fusion transcript was identified in one case. SNP-array analyses revealed the underlying event to be an interstitial deletion in the short arm of chromosome 5 (5p15.33). TERT was dramatically upregulated under the influence of the... (More)
Clear cell sarcoma of the kidney (CCSK) is a rare tumor type affecting infants and young children. Most CCSKs display few genomic aberrations, and no general underlying mechanism for tumor initiation has yet been identified, although a YWHAE-NUTM2B/NUTM2E fusion gene has been observed in a minority of cases. We performed RNA-sequencing of 22 CCSKs to investigate the presence of additional fusion transcripts. The presence of the YWHAE-NUTM2B/NUTM2E fusion was confirmed in two cases. In addition, a novel IRX2-TERT fusion transcript was identified in one case. SNP-array analyses revealed the underlying event to be an interstitial deletion in the short arm of chromosome 5 (5p15.33). TERT was dramatically upregulated under the influence of the IRX2 promoter. In line with TERT expression being driven by active IRX2 regulatory elements, we found a high expression of IRX2 in CCSKs irrespective of fusion gene status. IRX2 was also expressed in human fetal kidney - the presumed tissue of origin for CCSK. We conclude that in addition to promoter mutations and epigenetic events, TERT can also be activated in tumors via formation of fusion transcripts. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Cancer Letters
volume
357
issue
2
pages
498 - 501
publisher
Elsevier
external identifiers
  • pmid:25481751
  • wos:000349592200008
  • scopus:84920844167
ISSN
1872-7980
DOI
10.1016/j.canlet.2014.11.057
language
English
LU publication?
yes
id
ccc78b0a-0b95-4fa1-970f-2b546079148a (old id 4909545)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/25481751?dopt=Abstract
date added to LUP
2015-01-10 13:03:20
date last changed
2017-08-13 03:15:33
@article{ccc78b0a-0b95-4fa1-970f-2b546079148a,
  abstract     = {Clear cell sarcoma of the kidney (CCSK) is a rare tumor type affecting infants and young children. Most CCSKs display few genomic aberrations, and no general underlying mechanism for tumor initiation has yet been identified, although a YWHAE-NUTM2B/NUTM2E fusion gene has been observed in a minority of cases. We performed RNA-sequencing of 22 CCSKs to investigate the presence of additional fusion transcripts. The presence of the YWHAE-NUTM2B/NUTM2E fusion was confirmed in two cases. In addition, a novel IRX2-TERT fusion transcript was identified in one case. SNP-array analyses revealed the underlying event to be an interstitial deletion in the short arm of chromosome 5 (5p15.33). TERT was dramatically upregulated under the influence of the IRX2 promoter. In line with TERT expression being driven by active IRX2 regulatory elements, we found a high expression of IRX2 in CCSKs irrespective of fusion gene status. IRX2 was also expressed in human fetal kidney - the presumed tissue of origin for CCSK. We conclude that in addition to promoter mutations and epigenetic events, TERT can also be activated in tumors via formation of fusion transcripts.},
  author       = {Karlsson, Jenny and Lilljebjörn, Henrik and Holmquist Mengelbier, Linda and Valind, Anders and Rissler, Marianne and Øra, Ingrid and Fioretos, Thoas and Gisselsson Nord, David},
  issn         = {1872-7980},
  language     = {eng},
  number       = {2},
  pages        = {498--501},
  publisher    = {Elsevier},
  series       = {Cancer Letters},
  title        = {Activation of human telomerase reverse transcriptase through gene fusion in clear cell sarcoma of the kidney.},
  url          = {http://dx.doi.org/10.1016/j.canlet.2014.11.057},
  volume       = {357},
  year         = {2015},
}