Landscape analysis of urothelial carcinoma (UC) by telomerase reverse transcriptase (TERT) alterations


Tyler F. Stewart, Magalie Dosset, Pavel Brodskiy, Joanne Xiu, Arash Rezazadeh, Nataliya Mar, Sourat Darabi, Michael J. Demeure, Pedro C. Barata, Daniel M. Geynisman, Pooja Ghatalia, Monika Joshi, Chethan Ramamurthy, Chadi Nabhan, Elisabeth I. Heath, Hannah Carter, Maurizio Zanetti, Rana R. McKay


  • TERT is a catalytic subunit of telomerase, the unique enzyme that confers immortality to cells and is expressed in > 90% of cancer cells.
  • Mutations in the TERT promoter region (pTERTmut) are the most prevalent noncoding mutations in cancer.
  • TERT is self-antigen and is immunogenic first reported by the Zanetti lab at UCSD two decades ago and subsequently by many groups worldwide.
  • Immunogenic response to TERT are linked to improved outcomes for patients with cancer.
  • Data suggest patients with pTERTmut have worse clinical outcomes
  • However, small datasets suggest improved outcomes for patients with UC whose tumors harbor a pTERTmut when treated with immune checkpoint inhibitors
  • We evaluated the molecular and immune landscape of UC with and without pTERTmut.
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