01 Oct 2015 Chernobyl Tissue Bank Symposium

As part of the annual ESBB (European, Middle Eastern & African Society for Biopreservation & Biobanking) meeting, which this year was held in London, the CTB hosted a satellite meeting.

The meeting was held from 29th September – 2nd October 2015 and was hosted jointly by Imperial College and the Natural History Museum, London. For information about the meeting see http://www.esbb.org/london/index.html.

Abstracts of presentations at the CTB meeting on Thursday 1st October 10:30-12:15:

Overview and introduction             

Professor Gerry Thomas, Imperial College, London, UK

The Chernobyl accident in 1986 gave scientists around the world the opportunity to study what is normally a very rare type of cancer – thyroid cancer in young children and adolescents – and the opportunity to link environmental exposure of a carcinogen (in this case, radiation) to the molecular and clinical phenotype of the disease.  However, access to human samples is seldom easy, particularly when the samples come from young people in a different country.  The Chernobyl Tissue Bank (CTB) was established in 1998 to ensure that there was co-ordination of these studies and to provide infrastructure in Belarus, Ukraine and Russia to ensure that there was benefit to not only the wider scientific community, but also to the patients and to the local Institutes that were responsible for collection of the samples.  The CTB is supported by the governments of Ukraine and Russia, with financial support from the NCI of the US, the EC, Sasakawa Foundation of Japan and the WHO. The CTB was the first tissue bank of its type, providing multi-format, pathologically assured, biological samples to international research groups, and an infrastructure to track and collate research results from each individual sample with the aim of establishing a data repository for studies taking an “integrated biology” approach to understanding the mechanisms that underpin development of thyroid cancer.  The CTB provides a paradigm for biobanking in the “omics” era.

Turning a disaster to an opportunity - the CTB in Ukraine

Professor Tania Bogdanova, Institute of Endocrinology and Metabolism, Kiev, Ukraine.

The Chernobyl accident in Ukraine resulted in a significant increase of thyroid cancer in residents of Ukraine, Belarus and Russia exposed to 131-I in childhood and adolescence. The leading scientific centers of different countries showed an interest in the study of the resultant thyroid carcinomas.  The Chernobyl tissue bank (СТВ) was established in 1998 to facilitate access by the international research community to patient samples that were appropriately consented and pathologically verified, and to coordinate research activity to conserve a unique resource. The Ukrainian samples (3056 on 01.01.2015) comprise the majority (60%) of the samples collected in the СТВ and are the most requested samples for use in approved СТВ scientific projects. More than 2015 Ukrainian samples have been distributed to 30 leading centers of Europe, USA and Japan and have provided valuable new data on the molecular biology of thyroid carcinogenesis following radioiodine exposure.   More than 100 papers have been published using material from the CTB.

 

The major benefits for Ukraine in participating in the creation of the СТВ certainly allowed were a considerable improvement in the level of pathological diagnostics, due to purchase of modern equipment (embedding processors, cryostats, microtomes, microscopes, freezers), high quality reagents, using funds provided by the CTB.  The CTB also facilitated training of Ukrainian pathologists by world-leading pathologists and participation in the international pathology panel of СТВ. In addition, the CTB also provided opportunities for training many Ukrainian at world-leading scientific centres and participation in joint scientific projects allowed improvements in the level of Ukrainian science in the area of radiation pathology.

Thus, a nuclear disaster, in spite of its numerous tragic consequences, has become a powerful driver for increased scientific knowledge, and lead to improvements in the diagnosis of thyroid pathologies in Ukraine.   

Bioinformatic challenges to data enrichment of samples

Dr Sarah Butcher, Centre for Integrative Systems Biology and Bioinformatics, Imperial College, London, UK. 

Many areas of bio-research are becoming increasingly data-driven. Technological changes enable generation of higher and higher data volumes in more and more diverse areas, thus data are not just becoming larger, but also more complex and heterogeneous. Since the advent of systems approaches, researchers seek increasingly to combine datasets, (including legacy data), across different fields and sources and analyse them in ways perhaps unforeseen by the original generators.  To support these increasingly integrated ways of working, data associated with bio-samples needs to adhere to FAIR principles (findable, accessible, inter-operable and re-useable) if it is to be of optimal value.  Associating data generated from samples with the samples themselves can enhance the functional value of samples, by enriching the knowledgebase used to refine searches for suitable samples for further study, and by encouraging re-use of suitable datasets without duplication of effort and sample wasteage. Data may persist beyond the lifetime of a particular sample and this becomes particularly valuable where the sample was unique. The bio-data community maintains a wide range of data formats, standards, ontologies, and public repositories and this complexity can itself contribute to confusion over the most appropriate ones to use, as well as how to use them effectively. Different studies yield different datasets and the format in which data are held and represented can affect their re-useability both over time and for different audiences.  Here, we will discuss some of our practical experiences in encouraging data deposition in the framework of a tissue bank.

 

Systems biology approaches to radiation induced thyroid cancer.
Mark van de Wiel, VU University, Amsterdam, The Netherlands.

One of the most challenging problems in genomics is the construction or estimation of molecular networks from data. Such networks display how genes interact in a given condition, e.g. for a cancer cell. The challenge is two-fold: first, cope with the large number of possible interactions which is of the order p2 when studing p molecular features (e.g. genes) and second, the biological and or clinical interpretation of a network. I discuss several statistical methods to tackle both challenges, and illustrate the methods on several cancer genomics data sets.

 

The plan for comprehensive genomic characterization of radiation-related thyroid cancer in the Ukraine
Dr Meredith Yeager, National Cancer Institute, Bethesda, MD, USA. 

The thyroid glands of juveniles are highly susceptible to the carcinogenic effects of ionizing radiation.  Studies have established the high risk for papillary thyroid cancer (PTC) following iodine-131 exposure in children exposed after the Chernobyl nuclear accident. To date, the molecular signatures as well as the mechanisms underlying this association remain poorly understood. With >55% of post-Chernobyl PTCs attributed to I-131 exposure, we are conducting comprehensive genomic characterization to investigate the somatic and germline landscape of radiation-induced PTC. This opportunity has been accelerated by the completion of the Cancer Genome Atlas (TCGA) characterization of nearly 500 sporadic thyroid cancers in the USA, providing insights into possible thyroid cancer mechanisms. We have completed a pilot feasibility study of 12 PTCs cases from Ukraine with fresh frozen (FF), formalin-fixed paraffin-embedded thyroid tissues (FFPE), and blood. The success of the pilot establishes a strong scientific basis for extending this approach to a larger study of radiation-related PTCs from Ukraine. We will comprehensively characterize 500 PTCs drawn from the Ukraine (450 exposed and 50 unexposed) using biological samples (≥60% with FF tissue), individual dose estimates, and demographic characteristics available through the Chernobyl Tissue Bank. The primary objectives will be to complete an integrated characterization of the genomic, transcriptomic, and epigenomic landscapes of radiation-related PTCs for comparison with 500 sporadic PTCs available from TCGA; the study design will also enable the investigation of somatic changes across a spectrum of I-131 doses. 

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