New Strategies to Detect Cancers in Carriers of Mutations in RB1

Rationale: Individuals with a cancer predisposition due to a mutation in the paradigm tumor suppressor gene RB1, have a high risk to develop the childhood cancer retinoblastoma (Rb). Biopsies are not possible in Rb, before treatment selection. Heritable Rb patients have also a high risk to develop other types of second primary, either childhood or adult, malignancies (SPMs), notably sarcomas and melanomas. Remarkably, SPMs are now the leading cause of death in heritable-Rb-survivors. Unfortunately, there are no well-developed regular surveillance protocols for SPMs in Rb survivors available right now. Recently, new non-invasive cancer test have been developed, based on either RNA-sequencing data from platelets (ThromboSeq), or on extracellular membrane vesicles (EVs) derived from tumor cells present in blood. Objective: * Determine the non-cancerous baseline in adult RB1-mutation carriers (heritable-Rb-survivors). * Contribute to the biobanking of blood and cancerous tissues from RB1-mutation carriers with SPMs. * The development of blood-based tests, either platelet or EV-based, for the detection of (the type of) tumors in RB1-mutation carriers. Study design: Cross-sectional multicenter trial. Study population: * 40 Rb patients (children), * 40 controls (children), * 153 Rb survivors (adults), * 153 controls (adults), * 10 Rb survivors with SPM (children/adults). Main study parameters/endpoints: * Determine the non-cancerous baseline in adult RB1-mutation carriers (heritable-Rb-survivors). * Contribute to the biobanking of blood and cancerous tissues from RB1-mutation carriers with SPMs. Nature and extent of the burden and risks associated with participation, benefit and group relatedness: Two blood samples totalling 10ml blood will be collected for every participant. Additionally, a short questionnaire has to be filled in concerning their and their family's cancer history. Blood draws will be done, when participants are already present in the hospital for