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

作者：Karlsson Jenny^*; Lilljebjorn Henrik; Mengelbier Linda Holmquist; Valind Anders; Rissler Marianne; Ora Ingrid; Fioretos Thoas; Gisselsson David

来源：Cancer Letters, 2015, 357(2): 498-501.

DOI：10.1016/j.canlet.2014.11.057

• TERT
• IRX2
• RNA sequencing
• Pediatric kidney tumors
• Fusion transcript

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.

• 出版日期2015-2-28