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

Author:
  • Jenny Karlsson
  • Henrik Lilljebjörn
  • Linda Holmquist Mengelbier
  • Anders Valind
  • Marianne Rissler
  • Ingrid Øra
  • Thoas Fioretos
  • David Gisselsson Nord
Publishing year: 2015
Language: English
Pages: 498-501
Publication/Series: Cancer Letters
Volume: 357
Issue: 2
Document type: Journal article
Publisher: Elsevier

Abstract 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.

Keywords

  • Cancer and Oncology

Other

Published
  • ISSN: 1872-7980
Thoas Fioretos
E-mail: thoas.fioretos [at] med.lu.se

Principal investigator

Division of Clinical Genetics

+46 46 222 45 95

+46 70 334 33 67

BMC C13

66