Abstract

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• Introduction:

  Urothelial carcinoma (UC) is the fourth most prevalent malignancy in adults, accounting for 2.1% of cancer-related deaths. We aimed to describe the most frequent telomerase reverse transcriptase (TERT) gene mutations in this type of cancer and their relationship with the prognosis and treatment of this disease.

  Materials and methods:

  We performed a search strategy in Medline and Embase with the following keywords: telomerase reverse transcriptase (TERT) gene and upper tract UC. We included reviews and observational studies to support the statements throughout the manuscript.

  Results:

  The transcriptional activation of the TERT gene and subsequent telomerase activity is a prerequisite step in malignant transformation and progression. In advanced upper tract UC, TERT mutations are the most common genomic alterations in the Foundation Medicine database. C228T mutations predict distant metastasis in 60% of patients with renal pelvis cancer and 11% with ureteral cancer. Also, C228T and C250T mutations in urine DNA had a sensitivity of 87% and specificity of 94.7%. All TERT genomic alterations are inactivating short variant sequence mutations. There are no copy number gains or losses in TERT and no TERT gene rearrangements or fusions.

  Conclusions:

  Multiple markers, and mutations regarding the TERT gene and its promoter have been found in upper tract UC. The C250T and C228T mutations have shown promising results as diagnostic markers detected with urine tests.