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An international team involving scientists from the University of Nottingham has unveiled an innovative approach to understanding better the origin of cancer sub-types.
The team used high resolution comparative genomic information to investigate the biology that drives the formation of different variations of the disease.
This method was then used to create a laboratory model system which more accurately mimics the underlying disease and will, in turn, lead to the development of new drugs to target specific cancer variations far more effectively.
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Clinicians and scientists have long recognised that cancers may look the same under the microscope, but carry different mutations, respond differently to treatment and have markedly different outcomes for patients.
The research focused on a tumour of the brain and spine called Ependymoma which can affect both adults and children. In children, the prognosis is generally poor, particularly after a relapse and new and better treatments are urgently needed.
The new findings will be published in the prestigious scientific journal Nature on July 25 2010. It has been co-authored by Professor Richard Grundy, Professor of Paediatric Neuro Oncology and Cancer Biology at the University’s Children’s Brain Tumour Research Centre.
Professor Grundy said: “By matching genetic abnormalities identified within ependymomas arising in different age groups and locations of the central nervous system with the genetic signature of the cells from which these cancer are thought to develop, we have been able to create the first accurate laboratory model of this disease. This in turn can be used to identify new and more effective treatments for these patients. The next steps will be to start testing different drugs both alone and in combination and to develop models for the other ependymoma subgroups.”
For the study, investigators gathered 204 ependymomas from patients in the UK (on behalf of the Children’s Cancer and Leukaemia Group Biobank), the USA and Canada to conduct the most comprehensive analysis yet of the ependymoma genome.
Researchers found the pattern of DNA gain or loss differed depending on the ependymoma’s location in the brain or spine and uncovered nine subtypes of the disease. The analysis also identified more than 200 genes as potentially important for triggering the tumour or helping the cancer spread.
One of these was the gene EPHB2, which regulates stem cell division. In this study, investigators added extra copies of EPHB2 to a specific Neural stem cell which allowed a particular subtype of ependymoma to form. Using different methods, we were then able to show that these induced tumours were identical to a human ependymoma subtype. Adding extra copies of EPHB2 to other stem cells did not result in tumour formation. The research demonstrates for the first time that ependymomas in different regions of the nervous system arise when subtypes of stem cells found there acquire specific mutations.
Although the approach was developed by studying ependymomas, this strategy can potentially be translated to other forms of cancer.
The research was conducted in collaboration with scientists from St Jude Children’s Research Hospital, the University of Alabama and New York University Langone Medical Center in the US, The University of Newcastle, Seattle Children’s Hospital and the Hospital for Sick Children in Toronto.
The work was supported by the Joseph Foote Foundation. The Children’s Cancer and Leukaemia Group Biobank is supported by Cancer Research UK.
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Notes to editors:
The research has appeared in the July 18 advance online publication of Nature.
The University of Nottingham is ranked in the UK's Top 10 and the World's Top 100 universities by the Shanghai Jiao Tong (SJTU) and the Times Higher Education-QS World University Rankings.
More than 90 per cent of research at The University of Nottingham is of international quality, according to RAE 2008, with almost 60 per cent of all research defined as ‘world-leading’ or ‘internationally excellent’. Research Fortnight analysis of RAE 2008 ranks the University 7th in the UK by research power. In 27 subject areas, the University features in the UK Top Ten, with 14 of those in the Top Five.
The University provides innovative and top quality teaching, undertakes world-changing research, and attracts talented staff and students from 150 nations. Described by The Times as Britain's “only truly global university”, it has invested continuously in award-winning campuses in the United Kingdom, China and Malaysia. Twice since 2003 its research and teaching academics have won Nobel Prizes. The University has won the Queen's Award for Enterprise in both 2006 (International Trade) and 2007 (Innovation — School of Pharmacy), and was named ‘Entrepreneurial University of the Year’ at the Times Higher Education Awards 2008.
Nottingham was designated as a Science City in 2005 in recognition of its rich scientific heritage, industrial base and role as a leading research centre. Nottingham has since embarked on a wide range of business, property, knowledge transfer and educational initiatives (
www.science-city.co.uk) in order to build on its growing reputation as an international centre of scientific excellence. The University of Nottingham is a partner in Nottingham: the Science City