banda transcan 2 2016ul

Title: New strategies to detect cancers in carriers of mutations in RB1: blood tests based on tumor-educated platelets, or extracellular vesicles

Project Coordinator:
Josephine DORSMAN (The Netherlands) VU University Medical Center, Amsterdam

Project Partners:
Annette MOLL (The Netherlands) VU University Medical Center, Amsterdam
Petra TEMMING (Germany) University Hospital Essen, Essen
Francois DOZ (France) Institute Curie, Paris
Aurelien DE REYNIES (France) Ligue National Contre le Cancer, Paris

Project Abstract:
Background. RB1 is a paradigm gene for heritable cancer. Almost all RB1 mutation-carriers develop retinoblastoma (heritable-Rb-patient) during childhood and many heritable-Rb-survivors develop second primary malignancies (SPMs; notably sarcomas and melanomas) throughout life, which are often fatal. To date, no standard protocols are available for early detection of SPMs. Recently, blood-based cancer tests have opened up encouraging new possibilities for surveillance. We have developed novel non-invasive tests, that exploit the diagnostic power of either Tumor Educated Platelets (TEPs) or extracellular vesicles (EVs).
Hypothesis. Blood-based methods may be exploited in surveillance strategies for individuals with a heritable cancer predisposition. Non-cancer baseline in heritable-Rb-survivors might already differ from control individuals.
Aims. The aim of this project is to develop non-invasive blood tests, either platelet- or EV-based, for early detection and stratification of tumors in RB1-mutation carriers (NIRBTEST: Non-Invasive RB1 cancer TEST). As secondary aims, we will i) initiate the systematic and comprehensive biobanking of blood and cancerous tissues from RB1-mutation carriers with SPMs and ii) determine non-cancerous (no-SPM) baseline in heritable Rb-survivors.
Methods. I) Three sites will collect applicable clinical information. II) Blood will be collected from 153 adult RB1-mutation carriers without SPMs. IIa) RNA isolated from platelets will be analysed with next generation RNA sequencing. The RNA profiles of RB1-mutation carriers will be compared to 153 control individuals. IIb) DNA will be isolated from EVs and tested for allelic imbalances at the RB1 locus and compared to 153 controls. III) Blood will be collected from 40 children with Rb and compared to 40 pediatric control samples. Again platelet-derived RNA and EV-derived DNA will be isolated. Subsequently, we will determine whether Rb can be detected via blood based tests. IV) For participating individuals presenting with SPMs (either pediatric or adult), we will analyse the platelet-derived RNA or EV-derived DNA (pilot) and biobank cancer specimens.
Expected results and potential impact. This study will yield baseline levels for the platelet- and the EV- test in heritable-Rb-survivors. Moreover, we will determine whether these tests can be used for Rb detection/stratification. Importantly, these studies will set the stage for the use of blood-based tests for the detection of SPMs. The obtained results are expected to enhance the development of non-invasive cancer tests in general. The unique collaboration between fundamental researchers, clinicians from national Rb-reference centers, complemented with inventors of innovative cancer blood tests will strongly contribute to the success of the project.

 

 

(Project funded under JTC 2016)


TRANSCAN News

Launch of the call: JTC 2021
The new TRANSCAN-3 project consortium is launching the first Joint Transnational Call for proposals, co-funded by the European Commission, on:
"Next generation cancer immunotherapy: targeting the tumour microenvironment"

International Networking Event (virtual)
on 22 April 2021 hrs 9:00 CET
will focus on the forthcoming co-funded JTC 2021 on:
"Next generation cancer immunotherapy: targeting the tumour microenvironment" 
the event is organized by TUBITAK under the “Turkey in Horizon 2020 Phase II” Technical Assistance Project
in cooperation with TRANSCAN-3

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

 

eu flagship

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

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