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Nottingham scientists help unlock genetic secrets of cancer variations

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.

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 were published in the prestigious scientific journal Nature on July 25 2010. It was 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.

Top photo courtesy of Scene Photography.

Source:www.alumni.nottingham.ac.uk|

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