The European tissue bank and database GENEPI-ENTB is dedicated to research in radiation effects and in the genetic determinants of the variation in individual radiosensitivity. The primary aim of GENEPI-ENTB was to create a tissue bank linked to a detailed outcome-database of a large cohort of patients receiving radiotherapy and the development of a lymphocyte tissue bank containing samples from a cohort of large kindred French families, equally linked to a database. For that reason it was planned to establish a central database providing links to existing decentral databases and tissue banks, enabling optimal utilisation and access to data and material. It was GENEPI-ENTB's aim to network this way fragmented research efforts, to open up often dormant resources in comprehensive cancer centres for well equipped laboratories with no access to clinical facilities (such as nuclear research centres) and to create a high quality shared infrastructure for projects dedicated to radiation research.
To guarantee the quality of GENEPI-ENTB, dummy runs with modern statistical tools were planned to monitor the quality of this novel research infrastructure as well as the development of protocols for outcome assessment, tissue handling, and use and access of the infrastructure.
Another objective of GENEPI was to create a frame of reference for researchers who want to exchange tissue in the context of the GENEPI resource and to address the relevant ethical and legal issues to ensure that the project would be handled in compliance with all existing legislation and appropriate legal and ethical standards.
In the design of the project following challenges had to be given due consideration:
- The need to collect a number of tissues sufficiently large for gene pattern recognition even if some of the activated genes are very rare.
- The need to draw on a geographically spread research network to account for regional variations resulting from genetic drift.
- The daunting complexity of the ethical issues involved.
- The bio-informatics and ontology problems to be faced for the proper documentation in a central database of treatment parameters to be extracted from a variety of software systems, the tutorial effort required for the use of common procedures and internationally validated outcome data recording and finally the capacity for effective and user-friendly handling of queries and data retrieval.
Late radiation effects are progressive and may become a major clinical liability only after 10 to 15 years. For an earlier kick off of GENEPI supported research, it would be necessary to include besides prospectively collected samples (yielding interesting data only in the next decade), tissues stored earlier in the framework of high quality RT trials for which late response data are already documented.
It is planned that the GENEPI tissue bank will remain open for at least 20 years for accrual and access to tissues needed for research specifically addressing issues of radiation protection such as radiosensitivity. Besides its paramount importance for applied genomics research for the optimisation of RT, it will be an extremely valuable resource for the investigation and management of health risks associated with occupational, environmental and medical exposures at all dose levels. The infrastructure is designed to be used for different applications and study groups with minor adaptations. Already now new applications are developed and several study groups are interested and plan to use the web based database infrastructure.
Concrete examples of potential spin-offs of GENEPI enabled research could include predictive assays for radiosensitivity grading, molecular modulation of radiation response and tools for the improved radioprotection of individuals. Such innovations could be important contributors to cost-efficient health-care delivery. Beyond this, there may be realistic perspectives for commercial applications and exploitation underpinning the long term financial sustainability of the infrastructure.
In this context it can be mentioned that, pre-treatment gene expression profiling by microarrays in tumours has already been demonstrated to have an important predictive value for the progression of disease (e.g. with regard to rapid metastatic spread), although studies specific to the outcome of radiotherapy are still lacking.
Link to the GENEPI Entb1 Charter
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