1. Solving the genetic aetiology of hereditary gastrointestinal tumour syndromes- a collaborative multicentre endeavour within the project Solve-RD
- Author
-
Anna K. Sommer, Iris B.A.W. te Paske, José Garcia-Pelaez, Andreas Laner, Elke Holinski-Feder, Verena Steinke-Lange, Sophia Peters, Laura Valle, Isabel Spier, David Huntsman, Carla Oliveira, Richarda M. de Voer, Nicoline Hoogerbrugge, Stefan Aretz, Gabriel Capella, Gareth Evans, Andreas Rump, Evelin Schröck, Alexander Hoischen, Nicoline Geverink, Marc Tischkowitz, Leslie Matalonga, Steven Laurie, Christian Gilissen, Wouter Steyaert, and German Demidov
- Subjects
Genetic tumour risk syndromes ,lnfectious Diseases and Global Health Radboud Institute for Molecular Life Sciences [Radboudumc 4] ,Omics ,Metabolic Disorders Radboud Institute for Molecular Life Sciences [Radboudumc 6] ,Genomics ,General Medicine ,European reference network ,Tumour predisposition syndromes ,All institutes and research themes of the Radboud University Medical Center ,Neoplastic Syndromes, Hereditary ,ERN GENTURIS ,Exome Sequencing ,Tumours of the digestive tract Radboud Institute for Molecular Life Sciences [Radboudumc 14] ,Genetics ,Humans ,Genetic Predisposition to Disease ,Colorectal Neoplasms ,Cancer genetics ,Genetics (clinical) - Abstract
Background: Patients and families with suspected, but genetically unexplained (unsolved) genetic tumour risk syndromes lack appropriate treatment and prevention, leading to preventable morbidity and mortality. To tackle this problem, patients from the European Reference Network on Genetic Tumour Risk Syndromes (ERN GENTURIS) are analysed in the European Commission's research project "Solving the unsolved rare diseases" (Solve-RD). The aim is to uncover known and novel cancer predisposing genes by reanalysing available whole-exome sequencing (WES) data of large cohorts in a combined manner, and applying a multidimensional omics approach. Approach: Around 500 genetically unsolved cases with suspected hereditary gastrointestinal tumour syndromes (polyposis, early-onset/familial colorectal cancer and gastric cancer) from multiple European centres are aimed to be included. Currently, clinical and germline WES data from 294 cases have been analysed. In addition, an extensive molecular profiling of gastrointestinal tumours from these patients is planned and deep learning techniques will be applied. The ambitious, multidisciplinary project is accompanied by a number of methodical, technical, and logistic challenges, which require the development and implementation of new analysis tools, the standardisation of bioinformatics pipelines, and strategies to exchange data and knowledge. Results: and Outlook. The first re-analysis of 229 known and proposed cancer predisposition genes allowed solving 2-3% of previously unsolved GENTURIS cases. The integration of expert knowledge and new technologies will help to identify the genetic basis of additional unsolved cases within the ongoing project. The ERN GENTURIS approach might serve as a model for other genomic initiatives. This project has received funding from the European Union's Horizon 2020 research and innovation programme under grant agreement No. 779257 (Solve-RD). This study makes use of data shared/provided through RD-Connect, which received funding from the European Union Seventh Framework Programme (FP7/2007–2013) under grant agreement No. 305444.
- Published
- 2022