Activation of human telomerase reverse transcriptase through gene fusion in clear cell sarcoma of the kidney.
(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)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/4909545
- author
- 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
- organization
- publishing date
- 2015
- 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
- pmid:25481751
- 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
- 2016-04-01 10:34:36
- date last changed
- 2022-02-25 03:01:04
@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}}, doi = {{10.1016/j.canlet.2014.11.057}}, volume = {{357}}, year = {{2015}}, }