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

Summary, in English

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: Jenny Karlsson; Henrik Lilljebjörn; Linda Holmquist Mengelbier; Anders Valind; Marianne Rissler; Ingrid Øra; Thoas Fioretos; David Gisselsson Nord
• Department/s: Division of Clinical Genetics; BioCARE: Biomarkers in Cancer Medicine improving Health Care, Education and Innovation; Paediatrics (Lund)
• Publishing year: 2015
• Language: English
• Pages: 498-501
• Publication/Series: Cancer Letters
• Volume: 357
• Issue: 2
• Links: http://www.ncbi.nlm.nih.gov/pubmed/25481751?dopt=Abstract; http://dx.doi.org/10.1016/j.canlet.2014.11.057
• Document type: Journal article
• Publisher: Elsevier
• Topic: Cancer and Oncology
• Status: Published
• ISBN/ISSN/Other: ISSN: 1872-7980