Welcome to Issue 15 of the Biological Studies Newsletter.  This issues contains the usual information on tissue registration, current applications and diary dates and also includes an update on a current study - 2002 BS 03, an update on the IT infrastructure for the Tumour Bank and a report from Gail Jenner and Sarah Leigh Carr on their visits to Centres to support Tumour Banking.

  NCRI Meeting
  9th-10th October 2006, Birmingham

In response to feedback from the January meeting, we hope to have an all day session to encompass our clinical and scientific remit.

The morning clinical session will focus on presentations of national and international trials from the UKCCSG plus invited speakers.  The topics suggested so far include:

• Increasing incidence of childhood cancer – Jan-Willem Coeburgh
• European trials: Time for expansion into ‘New Europe’ – Kathy Pritchard-Jones

The afternoon session will concentrate on scientific presentations:

• Medulloblastoma – Richard Gilbertson
• Rhabdomyosarcoma – Janet Shipley
• Osteosarcoma – Lee Helman
• AML – Brenda Gibson

We are inviting abstracts for oral and poster presentations, for which the deadline is the 7th May and we urge you to support this important initiative.  This programme is still provisional, but we will keep you updated.

Paediatric Germ Cell Tumour Biological Studies Update

“Every scientific statement must remain tentative forever”, Sir Karl Popper 1934: in The Logic of Scientific Discovery; although I hope I can be a bit more definite in detailing progress in the germ cell field. There has been some advancement in the biology and the understanding of this rare and complex tumour group, although most of this relates to adult tumours. Interestingly, a new biologically based classification system has been proposed separating this tumour group into 5 types (Oosterhuis and Looijenga, Nat Rev Cancer. 2005 Mar;5(3):210-22). Whilst this is an exciting development it has yet to demonstrate any application in the treatment of germ cell tumours.

Research on paediatric germ cell tumours is progressing steadily. In the UK, funding for UKCCSG 2002 BS 03 (James Nicholson, Nick Coleman & Roger Palmer) has been secured until September 2008 and work to advance the initial pilot and interim study is well underway. So it’s all steam ahead once more in Cambridge. I would like to thank CLIC Sargent and the Medical Research Council for their funding of the research, and the generous support of the UKCCSG and all the centres that contribute to the tumour bank. We have now received 92 frozen paediatric germ cell tumour specimens from the UKCCSG, and an additional 8 specimens from European collaboration with Dr Dominik Schneider in Düsseldorf. In Cambridge, we have analysed 38 of these tumours so far. A novel gene list has been produced, from the expression array data, which discriminates between yolk sac tumours and germinomas. Furthermore, the genes discovered substantially differ from those produced in the recently published adult array studies. Watch this space!

Dominik Schneider has made a successful application for tissue through the UKCCSG Biological Studies Group to look at promoter methylation of SFD1/CSCR4 in extragonadal germ cell tumours (UKCCSG 2005 BS 07) in collaboration with James Nicholson at Cambridge. International collaboration of tumour material is essential for continued success in the investigation of this rare tumour group and the UKCCSG Germ Cell Tumour Group is now firmly established in this process. The mysteries behind how these rare tumours arise, and how treatments may be better directed may not be quite so far off now that research in this area is gathering pace.

Roger Palmer
MRC Cancer Cell Unit, Cambridge

Biological Studies IT Infrastructure

Significant progress has been made to the biological studies IT infrastructure, and we take this opportunity to update you on work behind the scenes. 

Searchable Website

Our first project is a searchable website that will give users unprecedented access to an anonymised version of our tumour bank, via the members area of the UKCCSG website.  Potential applicants will therefore be able to see the number of samples that could be made available for their research project.  And of course, those of you already running research projects will be able to track the accrual of new samples in to the back that could be used in your research.  This is almost ready to go onto the UKCCSG website for beta testing by our members.  Remember this is still version 1, so please be kind with your comments and suggested improvements.

A New Tumour Bank Database

It’s been a long time coming but we are now well on our way to completing the new tumour bank database.  This new database is not simply an upgrade, but a complete re-write.  Importantly, this database will use the 3 part codes as described in the new tumour banking protocol (2005 BS 01).
In contrast to our old database, the new system allows for complete flexibility when registering material into the tumour bank, so that we know at a glance exactly what tissue is registered from each patient.  It will also effectively track the registration, request and release of not only every sample, but every aliquot for each sample.  To make the most effective use of this very limited resource it will allow for the re-release of an aliquot.  In addition, it will also allow for the registration and release of tissue derivatives (DNA, RNA and protein) and is able to track this back to the parent aliquot.

As this database was built in house, it incorporates a previously developed matching programme that allows for seamless integration with the UKCCSG clinical trial databases and UKCCSG Registry.

Gavin Whyman

Reports from our roving tumour banking/biological studies team

Gail Jenner – Research nurse from Cambridge working 1 day per week for UKCCSG on Tumour Banking and Biological studies

Sarah Leigh-Carr – Biomedical scientist working with David Ellison primarily co-ordinating CNS samples for pathology review and also collecting samples for CNS biological studies and with a remit for supporting tumour banking as a whole.

Together we have been organising visits to centres that have ethical approval or who have shown an interest in participating in tumour banking.  The primary aim of these visits is not to ‘inspect’ but to meet and support personnel involved in the process of consenting, storing, registering and releasing samples.  In so doing we can put names to faces and get to know each other.  This we feel will facilitate better communication and raise awareness that we are in post as a support service to advise and help where appropriate.  The visits involve introducing/educating us to a variety of systems already in place whereby centres manage to co-ordinate the complicated process of banking tissue and subsequently releasing to researchers. This has helped us to have a clearer understanding of systems in each centre and enabled us to pass on tips to other centres.  We are also now familiar with the local staff involved which has paved the way for much better communication.

Visits to date have included Newcastle, Cambridge, Sheffield, Royal Marsden, Aberdeen and Birmingham.  We thank those centres for allowing us to cross the threshold and for giving up their valuable time to show us around.  All the visits have all been very informative and we hope we have been able to deal with queries raised in a satisfactory fashion.  We have prepared reports for each centre following the visit and circulated this to all personnel to confirm all points raised and answers to queries.

As a direct result of these visits Sheffield have now started to bank blood samples in Leeds, and Aberdeen have started to register samples already stored locally.

We hope that by meeting all the clinical and lab staff together local issues can be clarified and the result will be a more cohesive team approach.   These visits have provided us with a far greater insight into the finer details and practical aspects of tumour banking and we have both learnt a huge amount; we hope that the centres visited have also gained benefit from this exercise. We look forward to continuing our visits (there are more arranged) and would like to take this opportunity to re-iterate that we (along with Gavin Whyman) are always available to address queries and concerns – our contact details are as follows.

Gail Jenner, Research Nurse (UKCCSG Mondays, also available at Addenbrookes, Cambridge) gpj2@le.ac.uk and gail.jenner@addenbrookes.nhs.uk
Sarah Leigh Carr, Biomedical scientist S.L.Carr@ncl.ac.uk
Gavin Whyman, Biological Studies Data co-ordinator gavin.whyman@le.ac.uk

Biological Studies Applications
http://www.ukccsg.org/public/biological_studies/appforms.html

Current applications:

Four new applications were received in the November round and 3 in the February round:-

Dr G Strathdee & Dr S Meyer – Analysis of DNA- methylation of genes involved in control of differentiation. 
This has been reviewed internally and externally.  The reviews were generally positive but some issues were raised and Dr Strathdee has been asked to respond to these.

Dr André Oberthuer – International Neuroblastoma Trial for the Evaluation of Gene-expression based Risk classification and Tumour behaviour Estimation (INTEGRATE).
As this has already been reviewed by a grant funding body, external reviews were not required.  Internal reviewers have been received and a response is being prepared.

Dr Michael Jackson - Application of SNP chips to constitutive DNA samples to assess genomic copy number in neuroblastoma.
This was an application for just two samples and was therefore reviewed by the committee and approved.

Dr Janet Shipley – Comprehensive molecular analysis of tumour samples from patients entered onto previous and current European rhabdomyosarcoma clinical trials.
This has been reviewed internally and externally and again reviews were generally very positive.  Some queries were raised and response is awaited.

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.
This has been sent for internal review.  It has already had external peer review and copies of the reports have been forwarded to internal reviewers.

Dr Sally Kinsey – Investigation of the role of PMS2 gene in childhood leukaemia.
Has been sent out for internal and external review.

Studies recently approved:

Dr Michael Sullivan – The pathogenesis and prognostic stratification of hepatoblastoma (and hepatocellular carcinoma) by microarray gene expression analysis.

Dr MA Buendia – Predictive value of the analysis of gene expression profiles in hepatoblastoma.

These two applications have both been approved subject to prioritisation by the Chair of SIOPEL.

The next submission date is 15th May.

Diary Dates 2005

Wednesday 14th June - Meeting, Data Centre Leicester
Tuesday 5th September - Conference call
Thursday 16th November - Meeting, 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 at the end June 2006.  If you have any items that you would like to include, please send them to Sue Thornton at st22@le.ac.uk by 21st June 2006.

Chair Division of Biological Studies Prof Richard Grundy University of Nottingham Queen’s Medical Centre Tel: 0115 970 9257 Fax: 0115 970 9382 e-mail: richard.grundy@nottingham.ac.uk

Biological Studies Coordinator Gavin Whyman UKCCSG Data Centre, Leicester Tel: 0116 249 4471 Fax: 0116 254 9504 e-mail: gavin.whyman@le.ac.uk

Biological Studies Admin Sue Thornton, UKCCSG Data Centre, Leicester Tel: 0116 249 4463 Fax: 0115 254 9504 e-mail: st22@le.ac.uk