UKCCSG Biological Studies Newsletter - Autumn 2006
Issue: 16
Welcome to Issue 16 of the Biological Studies Newsletter. This issue contains the usual information on tissue registration, current applications and diary dates and also includes an update on the tumour bank and an update on AML research.
UKCCSG – UK CLWP Merger
As of 1st August the UKCCSG and UK CLWP have merged to become CCLG – Children’s Cancer and Leukaemia Group. New logo and branding are now being finalised and will be incorporated into the next newsletter.
NCRI Cancer Conference - 9th-10th October 2006, Birmingham
The paediatric section of the NCRI conference is split over two days with Translational Biology on 9th October from 15.15 to 17.30 and Paediatric Oncology – Clinical Trials on 10th October, again from 15.15 to 17.30.
The programme for the two sessions is shown below and full details can be found on the NCRI website - www.ncri.org.uk/ncriconference/.
Please support this conference!!
Paediatric oncology - Translational biologyMonday 9 October - 15:15 - 17:30 |
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Translational biology and paediatric neuro-oncology: |
New therapy concepts for neuroblastoma: successful in vitro results with small-molecule MDM2 antagonist nutlin-3 and the search for new molecular targets using genome wide analysis of tumour cells and foetal neuroblasts Blastemal expression of IGF1R in Wilms tumours is driven by increased copy number and correlates with relapse – Proffered Paper Presentation |
Paediatric oncology - Clinical trialsTuesday 10 October - 15:15 - 17:30 |
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A new international therapeutic classification for neuroblastoma The Children's Oncology Group CNS studies: strategy, progress and plans for the future |
Acute lymphoblastic leukaemia 2006: the COG paradigm EICESS-92: A successful collaborative intergroup trial in Ewing’s Sarcoma with unexpected results Cancer incidence in relatives of children with osteosarcomas and chondrosarcomas - Proffered Paper Presentation |
The CCLG tumour bank: Current status and future directions
The CCLG tumour bank represents a significant and valuable resource for research in paediatric tumours in the UK, for which I have recently taken over as Chief Investigator from Professor David Ellison. Currently, the tumour bank contains over 5,000 specimens including both frozen material and paraffin sections, which are available to numerous research groups for a range of biological studies projects. The accrual of this large collection of specimens is a testament to the work of the many individuals involved.
Despite the impressive total number of specimens banked to date, there are still several issues which must be addressed. First, it is apparent that the release of samples for a specific project causes a significant workload for many individual centres, which must be centrally coordinated, a process which sometimes leads to delays in release of samples to researchers. We are therefore currently exploring the possibility of holding all samples in a centralised CCLG tumour bank. This would potentially allow both easier monitoring of sample availability and usage in addition to forming a more efficient distribution point. However, there are several practical issues which need to be explored to determine whether such an approach is feasible, not least of which is the availability of such a bank and costings, both of which are being investigated at present.
Secondly, as many may already be aware, all centres dealing with human tissue of any kind for research use now require licensing with the human tissue authority (HTA) to take effect from the first of September 2006. Following discussions with the HTA, it has not been possible for CCLG to apply for a generic licence to cover all centres and therefore each individual centre banking tissue for research requires its own licence. This is associated with a potentially significant increase in workload and cost for those centres involved and CCLG is extremely grateful to all the individuals who have participated in the HTA licensing process at the participating centres.
Thirdly, over the past year, numerous site visits have been carried out to the individual centres by Gail Jenner and Sara Leigh Carr in order to identify specific practical problems which may be preventing the optimal banking of specimens. This process has been extremely useful and has highlighted the range of difficulties that are present in different centres, ranging from practical problems with sample storage within the histopathology department through to problems with the systems of obtaining or recording patient consent for banking. It is anticipated that a coordinated response from the biological studies committee of CCLG will hope to address many of these issues in the coming year in order to improve banking efficiency.
It is therefore apparent that whilst the tumour bank continues to represent a potentially unique and highly valuable resource for research into paediatric tumours, CCLG must continue to try to optimise banking from all centres of both frozen and paraffin embedded material and make the whole process of tissue banking as painless as possible for the centres involved. It is recognised that participation in this process, which is vital for its ongoing success, is dependent upon extra work and dedication of the individuals within each centre. Given that there are the issues noted above which will potentially require some changes to the way banking is carried out, in addition to possible changes in the consent process, and more widespread central pathological review for tumour specimens, CCLG plans to hold a meeting for all interested biomedical scientists, research nurses, clinicians and pathologists across centres in the coming months to address all of these issues in order that the tumour bank continues to develop and fulfil it’s purpose.
Neil Sebire
Consultant Paediatric Pathologist
Great Ormond Street Hospital
Dissecting the biology of DS-AMKL
Though tremendous strides have been made in the treatment of childhood leukaemia, ~40% of children with AML die from their disease. Thus, there is still a great need to understand the biological basis of the disease to enable more targeted and less toxic therapies to be developed. Over the last three four years there has been an explosion in our understanding of one particular type of AML that may open the field for this goal to be achieved.
For years now it has been clear that though children with Down Syndrome (DS) are not cancer prone in general, they have a 150-fold increased risk of developing AML compared to the general paediatric population. In most cases this AML is megakaryocytic. Moreover, the AML they develop has a fascinating natural history. At least 10-20% of DS neonates develop a clonal myeloid pre-leukaemic disorder, Transient Myeloproliferative Disorder (TMD) (also known as Transient Abnormal Myelopoiesis, TAM). ~30% of neonates with TMD subsequently develop AML. TMD and AMKL are also linked molecularly. In 2004, through a national collaboration of paediatric haematologists in the UK and Ireland we showed acquired somatic mutations in the key megakaryocyte transcription factor GATA1 were specifically present in both AMKL and TMD. Moreover, patients who progress from TMD to AMKL have the same GATA1 mutation at both stages. This makes biological sense as normal GATA1 function is critically required to ensure that megakaryocyte lineage cells mature properly both in human patients and in animal models. Emerging data from these animal models shows that the mutations in GATA1 of the type seen in DS AML are likely to incapacitate GATA1’s ability to stop abnormal proliferation of megakaryocyte precursors.
Based on these studies, we have been fortunate to receive funding from the Leukaemia Research Fund to investigate exactly how haemopoietic differentiation is perturbed in surplus diagnostic bone marrow samples from children with DS who develop AML. In parallel collaborative studies Irene Roberts (Hammersmith Hospital, London), Helena Kempski and David Webb (Great Ormond Street), Brenda Gibson (Glasgow) and Eve Roman and Sally Kinsey (York and Leeds) are studying different biological aspects of these disorders. Though DS AML is rare the sum of these studies will provide a detailed insight into paediatric pre-leukaemia and leukaemia and hopefully delineate the stage(s) of haematopoiesis where cell fate may be corrupted to give rise to leukaemia.
These studies in DS AML have UKCCSG peer-reviewed approval and Trent MREC approval. All we will require is a sample from diagnostic bone marrow that is surplus to clinical requirements. The sample can be collected as usual in an EDTA tube or even better in a bottle that is used to send sample to the cytogenetics laboratory. As only 10-15 cases of DS AML present annually it is vitally important that we capture as many cases as possible.
For further details please contact Dr Vyas.
Paresh Vyas
Weatherall Institute of Molecular Medicine
Oxford
Biological Studies Applications
http://www.ukccsg.org/public/biological_studies/appforms.html
Studies under consideration:
Prof Richard Grundy – eTumour: web accessible MR decision support system for brain tumour diagnosis and prognosis, incorporating in vivo and ex vivo genomic and metabolomic data.
Dr Nicola Annels and Prof Martin Egeler – Genome-wide detection of possible chromosomal imbalances in LCH cells using BAC microarrays.
Studies recently approved:
Dr G Strathdee & Dr S Meyer – Analysis of DNA- methylation of genes involved in control of differentiation.
Dr André Oberthuer – International Neuroblastoma Trial for the Evaluation of Gene-expression based Risk classification and Tumour behaviour Estimation (INTEGRATE).
Dr Janet Shipley – Comprehensive molecular analysis of tumour samples from patients entered onto previous and current European rhabdomyosarcoma clinical trials.
Dr Sally Kinsey – Investigation of the role of PMS2 gene in childhood leukaemia.
Prof Richard Grundy – Cooperative research strategy for paediatric high grade glioma: comprehensive mapping of gene expression and genomic gains and losses in paediatric high grade glioma: a joint UKCCSG and Paediatric Brain Tumour Consortium (USA) study in association with the National Cancer Institute Neuro-oncology branch.
Dr Suzanne Turner – The role of NPM mutation/LOH in the development of anaplastic large cell lymphoma and other T-cell lymphomas.
Prof Mel Greaves – Development of human stem-cell model for MLL-AF4 leukaemogenesis.
Tissue Registration Update
| FFPE | Frozen | Total | |
| Adrenal Tumours | 26 | 26 | |
| Astrocytoma | 300 | 156 | 456 |
| Brain Stem Glioma | 20 | 9 | 29 |
| Choroid Plexus Carcinoma | 8 | 11 | 19 |
| Clear Cell Sarcoma | 23 | 28 | 51 |
| Ependymoma | 98 | 101 | 199 |
| Ewings | 27 | 55 | 82 |
| Germ Cell | 63 | 159 | 222 |
| Glioblastoma | 25 | 16 | 41 |
| Hodgkin's Lymphoma | 99 | 226 | 325 |
| LCH | 17 | 31 | 48 |
| Leukaemia | 20 | 17 | 37 |
| Liver Tumour | 20 | 76 | 96 |
| Medulloblastoma | 111 | 102 | 213 |
| Mesoblastic Nephroma | 8 | 15 | 23 |
| Misc Other (incl Benign) | 109 | 306 | 415 |
| Nasopharyngeal Carcinoma | 3 | 8 | 11 |
| Neuroblastoma | 146 | 648 | 794 |
| Non-Hodgkin's Lymphoma | 45 | 172 | 217 |
| Osteosarcoma | 16 | 37 | 53 |
| Pineal Tumour | 2 | 3 | 5 |
| PNET | 71 | 104 | 175 |
| Rhabdoid Tumour | 20 | 30 | 50 |
| Rhabdomyosarcoma | 116 | 205 | 321 |
| Sarcoma | 15 | 57 | 72 |
| Wilms | 418 | 621 | 1039 |
| Grand Total | 1800 | 3219 | 5019 |
Online CCLG Tumour Bank Search Engine
As part of our continuing IT development, I’m please to inform you that you can now remotely search the CCLG Tumour bank. A fully anonymised version of the database is available online and can be found at http://www.tissue-bank.org.uk. You can logon to the site using the same user name & password you use to access the members area of the UKCCSG website. If you are not a member of the CCLG/UKCCSG or have forgotten your password please contact me at gavin.whyman@le.ac.uk.
Gavin Whyman
Diary Dates 2006
Thursday 16th November
Morning meeting at 44 Lincoln’s Inn Fields, followed by joint meeting with Division of Therapeutics
Wednesday 13th December
Conference call
Newsletter distribution
This newsletter is distributed to all members of the Division of Biological Studies, UKCCSG Centre coordinators, UKCCSG Centre Data Managers, Research Nurses, Pathologists and Pathology personnel in Centres, and to all those on our database of scientists.
It is also available under the Biological Studies icon on the UKCCSG website – www.ukccsg.org.uk.
If you know of any other colleagues who may wish to receive a copy, please forward contact details to Sue Thornton, st22@le.ac.uk
NEXT EDITION ... The next issue will be sent out towards the end of the year. If you have any items that you would like to include, please send them to Sue Thornton at st22@le.ac.uk. |
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