Abnormal copies of chromosomes in the cells of ependymoma tumours
Recent research from Nottingham University (England, UK) indicates that a chromosomal abnormality in children with a deadly form of brain cancer is linked with a poorer chance of survival. The study led by experts at Nottingham's Children's Brain Tumour Research Centre may lead eventually to a new diagnostic test to allow doctors to identify children at the highest risk associated with an ependymoma tumour and who may, therefore, benefit from aggressive life-saving treatments.
This research could also help medical experts decide which children with an ependymoma tumour have a better prognosis and would benefit from less intensive therapies, reducing their exposure to a range of side effects which can cause permanent disabilities, having a debilitating impact on them for the rest of their lives.
The recent study (see Ref. below) focused on consideration of abnormal copies of chromosomes in the cells of ependymoma tumours. The researchers attempted to assertain whether or not this was associated with a more negative expectation for children suffering from the disease. They found that increased copies of a specific region of a chromosome called 1q25 were associated with approx 20% of the 147 tumours they tested from European children with ependymoma and that it was associated with a worse outcome in younger children treated with surgery and chemotherapy.
Predicting the future
When combining the results for 1q25 copy gain with how much tumour was removed at the time of surgery, the scientists accurately placed the children (patients) into three risk groups categorized as "high risk", "intermediate risk" and "standard risk".
Dr Kilday said:
" This study is the first to assess copy number gain like this in groups of children with ependymoma who have been treated in a similar way and is an important step forward in being able to predict the future for children with these brain tumours
_ We are now hoping that these findings are reproduced in other studies currently underway in other countries, including the USA" added Professor Grundy, "If their results match ours, then the presence of 1q25 copy gain in childhood ependymoma could be introduced into future international treatment planning as a new marker of poor outcome which will in turn define treatment. We would intend that this should be something each patient's tumour is tested for at the time of diagnosis."
Ependymomas are brain tumours that can occur at any age but are more common in children. Despite improvements in therapy over recent years, the prognosis for children with this cancer remains poor, sadly 40% of affected children still die.
According to medical experts, one of the reasons why survival for childhood ependymomas has not improved is that, until now, medical specialists have not been able to predict accurately which tumours will behave more or less aggressively than others.
- In normal humans, the cells which make up our body tissue contain chromosomes made up of DNA and proteins — the building blocks of life. Normally, our cells have two copies of 23 chromosomes (numbered 1 to 22) plus two sex chromosomes, making a total of 46 chromosomes. Each chromosome has two arms — a short arm called the p arm and a long arm called the q arm.
- In tumour cells the number of chromosomes can vary significantly from the normal cell numbers and in ependymoma a frequent finding from biological studies is increased copies of chromosome number 1, specifically increased numbers of the long arm of chromosome 1. This abnormality is termed 1q copy number gain.
In the case of the Nottingham University study, the scientists assessed the results from 147 brain ependymomas in young UK and French children who received tumour surgery followed by chemotherapy and older European children who received tumour surgery followed by radiotherapy.
Copy number gain of 1q in the ependymoma cells from each of the 147 patients was assessed using a technique called fluorescence in situ hybridisation (FISH) in which pieces of DNA called probes are made in the lab containing a fluorescent dye. This enables the tumour cells to be seen down a fluorescent microscope. In the Nottingham project, the scientists used a green probe that bound to a region within chromosome 1q of the tumour cells, called 1q25.
The team then linked which of the ependymomas had increased copies of the 1q25 probe in their cells to corresponding patient data to work out whether increased copy number gain was associated with a worse survival rate.
Ref. to Paper:
Copy number gain of 1q25 predicts poor progression-free survival for pediatric intracranial ependymomas and enables patient risk stratification. Clin Cancer Res clincanres.2489.2011 (http://bit.ly/H15unQ)
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Source: Nottingham University, England