banda transcan 2 2016ul

Title:
Comprehensive genomic characterization of upper urinary tract urothelial carcinoma and paired bladder recurrences

Project Coordinator:
Joost L. Boormans (Netherlands), Erasmus MC, Dept. of Urology, Rotterdam 

Project Partners:
Yves Allory (France), Institut Curie, Oncologie moléculaire, Paris
Bernardo Herrera (Spain), Virgen de la Victoria University Hospital, Dept. of Urology, Malaga
Arndt Hartmann (Germany), University Clinic Erlangen Institute for Pathology, Erlangen

Project Abstract:
Background: Upper urinary tract urothelial carcinoma (UTUC) patients have poor outcomes and a high risk of future urothelial carcinoma of the bladder (UCB) after radical surgery. Currently, diagnostic tools that predict the risk of a UCB recurrence are lacking and more effective therapies are needed to improve survival. This project envisions the identification of novel genetic leads for improved diagnostics and therapy by large-scale genomic characterization of UTUC and paired UCB recurrences as the solution to address these clinical needs.
Hypothesis: 1) UTUC and UCB recurrences are clonally related, enabling surveillance by molecular urine diagnostics. 2) UTUC is characterized by molecular alterations that lead to high tumor mutational burden (TMB), offering a target for immunotherapy.
Aims: Primary: to clarify the clonal origin of UTUC and paired UCB recurrences. Secondary: to identify genomic alterations of UTUC and to investigate the potential of these aberrations as novel draggable targets and predictors of response to therapy.
Methods: A retrospective cohort of 199 UTUC + 99 UCB recurrences (discovery set) and a prospective cohort of 170 UTUC samples (validation set) are compiled. Whole exome sequencing, microsatellite instability analysis, and immunohistochemistry are done to assess TMB, mismatch repair deficiency, immune infiltration and molecular subtypes. The genomic profile of UTUC and paired UCB is compared and molecular alterations of UTUC are correlated with clinical outcome and therapy response.
Expected results and potential impact: This project provides novel insights on the clonality of UTUC and paired UCB. This can be applied to replace cystoscopies by patient-friendly urine assays for surveillance after surgery. Moreover, it enables the identification of new actionable genomic changes of UTUC that serve as targets for therapy, such as precision-guided immunotherapy in UTUC patients with high TMB leading to durable responses and improved outcome.

 

(Project funded under JTC 2017)


TRANSCAN News

 Preliminary Announcement
The new TRANSCAN-3 project consortium is pre-announcing the first Joint Transnational Call for proposals, co-funded by the European Commission, on:
"Next generation cancer immunotherapy: targeting the tumour microenvironment"

ERA-NET Cofund TRANSCAN-3:
 Sustained collaboration of national and regional programmes in cancer research
is the new project funded by the European Commission under H2020  which started on 1st March 2021 and will last five years (G. A. no. 964264)

A TRANSCAN-2 brochure, highlighting key achievements, is available for download

 

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This project has received funding from the European Union’s Horizon 2020 research and innovation programme under grant agreement No 643638.