61P - Integrated molecular signatures of TERT promoter deregulation predict disease outcomes in non-muscle invasive bladder cancer

Date 11 September 2017
Event ESMO 2017 Congress
Session Poster display session
Topics Urothelial Cancers
Genitourinary Cancers
Translational Research
Presenter Ricardo Leão
Citation Annals of Oncology (2017) 28 (suppl_5): v1-v21. 10.1093/annonc/mdx361
Authors R. Leão1, D. Lee2, A. Figueiredo3, M. Komosa4, C. Zhang5, J. Apolónio4, N.M. Nunes4, T. Hermanns6, P. Wild7, C. Poyet6, R.J. Hamilton1, P. Castelo-Branco4, U. Tabori2
  • 1Surgical Oncology /urology, Princess Margaret Cancer Centre, M5G 2M9 - Toronto/CA
  • 2Hematology Oncology, The Hospital for Sick Children, M5G2k5 - Toronto/CA
  • 3Urology, Coimbra University Hospital, 300 - Coimbra/PT
  • 4Brain Tumour Research Centre, The Hospital for Sick Children, M5G2k5 - Toronto/CA
  • 5Brain Tumour Research Centre, The Hospital for Sick Children, Toronto/CA
  • 6Urology, Zurich University Hospital, 1111 - Zurich/CH
  • 7Pathology, Zurich University Hospital, Zurich/CH

Abstract

Background

Recent studies showed increased interest in telomere biology bladder cancer. These studies were mainly focused on hotspot TERT promoter mutations and their contribution for telomerase activation and clinical outcomes. However, the study of TERT promoter methylation, as an additional deregulatory mechanism of TERT expression, was not studied in this disease. We previously uncovered a region in the TERT promoter region (THOR – TERT hypermethylated oncological region) which is specifically hypermethylated and associated with telomerase activation in cancer tissue. In this study we aim to establish the value of this duet (TERT promoter mutations and THORMeth) in bladder cancer recurrence and progression.

Methods

To explore the impact of TERTpMut and THORMeth on TERT expression and clinical outcomes in UBC we studied two cohorts of UBC patients, 331 FFPE samples. THORMeth status was assessed using quantitative bisulfite pyrosequencing. Sanger Sequencing and ddPCR accessed TERTpMut status. TERT expression was evaluated by ddPCR. Cox proportional hazards models were used to correlate THORMeth and TERTpMut with disease recurrence and progression.

Results

THOR is a diagnostic marker for urothelial bladder cancer. THOR hypermethylated (n = 127, 53.6%) is associated with higher levels TERT expression (p 

Conclusions

THOR is a novel biomarker for UBC, and, as TERTpMut is able to predict disease recurrence in NMIBC. TERTpMut/highTHORMeth, comprises a distinct signature that is associated with disease progression and higher TERT expression. This fact suggests a hypothetical synergism between both mechanisms and highlights the merit of evaluating TERT promoter methylation as other deregulatory mechanism in TERT expression with implications in patients’ outcomes.

Clinical trial identification

Legal entity responsible for the study

Funding

Foundation for Science and Technology, Portugal, Individual Doctoral Grant SFRH/BD/102232/2014.

Disclosure

All authors have declared no conflicts of interest.