Ewing's sarcoma Biology

This information has been written for patients, their families and friends and the general public to help you understand more about Ewing's sarcoma: what it is and the different types. This information is produced in accordance with BCRT's information policy.



There has been a lot of research into the biology of Ewing's sarcoma in recent years, in order to help us to understand what causes cells to become cancerous; however there are still many un-answered questions. Recent research has been moving our knowledge forward but only very slowly.

We do know that cells contain important information in their chromosomes called genes, which instruct cells on how to divide and grow normally. Damage to certain genes can cause a cell to behave differently and grow abnormally, which can then lead to development of cancer.

We know that almost all Ewing's sarcoma patients share the same kind of gene damage, although we don’t know what causes this damage to happen.

Genes are made of a molecule called DNA. In cells, DNA is found in long strings called chromosomes. Each chromosome is made up of thousands of genes, one after another. We know that in Ewing's sarcoma there is a chromosomal translocation – this means that a part of a chromosome has broken off and stuck to the wrong chromosome, or sometimes there is a swap of sections of DNA between one chromosome and another.

Translocations put the genes in the wrong order along a chromosome and this can mean that genes are switched on and off wrongly, in a way that can cause cancer or other illnesses.

 
Chromosomes

In figure 3, you can see the chromosomes in a human cell. Humans have 23 pairs of chromosomes. Each pair contains 1 copy from the mother and one copy from the father (this is how we can inherit traits from both parents). One pair of chromosomes forms the ‘sex chromosomes’, and if a person has XY they are male or if they have XX they are female.

The chromosomes have are been given a number from 1 to 22 (the sex chromosomes are number 23). Chromosome 1 is the longest, 2 is slightly shorter, and so on to number 22, which is the shortest.

Figure 3. Diagram showing the full set of human chromosomes, which are long strings of DNA.

Figure 4 shows a microscope picture that shows the chromosomes as strings in the centre of a cell. The study of chromosomes is carried out by scientists known as cytogeneticists (SY-tow-geh-NET-eh-sist).

Figure 4. Microscope image of Cells Showing Visible Chromosomes inside cells.

 
Chromosome Translocations

In around 95% of Ewing's sarcoma cases, there is a translocation between chromosomes, and we know that this translocation causes the cancer to start.

The particular translocation in Ewing's sarcoma, PNET and Askin tumour is usually where a part of chromosome 11 has moved to chromosome 22 and a piece of chromosome 22 has moved to chromosome 11.

You may see this written as t(11;22)(q24;q11) when you are reading about Ewing's sarcoma. The 't' stands for translocation and the numbers in the first brackets tell us which chromosomes are involved. The second bit in brackets tells us what part of the chromosome is involved. Some Ewing's sarcoma patients have slightly different genetic changes. These are the translocations described as t(21;22)(q22;q12), t(7;22), t(17;22) or t(2;22) or a slightly different genetic change called inv(22).

 
How do chromosome translocations cause problems in cells?

When a translocation occurs, it interferes with the genes. Genes can be broken when the chromosomes break, so the genes can’t do their usual job in the cell. Alternatively, two genes can be stuck together where the chromosomes join together. This fuses two genes together, making a so called ‘fusion gene’, which has some properties of each gene. Either of these situations can cause cancer.

In the case of Ewing's sarcoma the translocation between chromosomes 11 and 22 joins two genes together, one called EWS and the other called FLI1, to form a 'fusion gene' called EWS-FLI1. Fusion genes are found in different cancers but EWS-FLI1 is specific to the Ewing's sarcoma Family of Tumours and can therefore help to confirm the diagnosis of Ewing's sarcoma.

The formation of the EWS-FLI1 fusion gene instructs the cell to make EWS-FLI1 fusion protein, which is a ‘transcription factor’. Transcription factors are powerful switches in the cell, able to switch many other genes on or off. EWS-FLI1 causes cancer by switching the wrong genes on and off at the wrong times, causing the cell to divide uncontrollably.

The EWS-FLI1 translocation happens only in the cells of the tumour. The translocation does not occur in sperm or egg cells and therefore people with Ewing's sarcoma can’t pass the translocation on to their children. This means that there is no increased risk of Ewing's sarcoma for the children of surviving patients. There is also no increased risk for brothers and sisters of Ewing's patients.

 
Why is research into the biology of Ewing's sarcoma important?

Research to identify the exact cell type in which the EWS-FLI1 translocation happens and Ewing's sarcoma starts is a big area of research. Knowing this could allow scientists and doctors to work out what causes the chromosome translocations to happen.

Understanding the biology of cancer cells helps doctors and scientists to find new targets for treatment and markers (clues) that can help a patient to be diagnosed quicker. For example, some researchers are trying to make new drugs that target EWS-FLI1 fusion protein, to allow all Ewing's sarcoma cells to be killed without harming healthy cells.


Ewing's sarcoma information Version 2, June 2013
Last reviewed: June 2013
Next review due: June 2015

The authors and reviewers of this information are committed to producing reliable, accurate and up to date content reflecting the best available research evidence, and best clinical practice. We aim to provide unbiased information free from any commercial conflicts of interest. This article is for information only and should not be used for the diagnosis or treatment of medical conditions. BCRT can answer questions about primary bone cancers, including treatments and research but we are unable to offer specific advice about individual patients. If you are worried about any symptoms please consult your doctor.

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BCRT shall hold responsibility for the accuracy of the information they publish and neither the Scheme Operator nor the Scheme Owner shall have any responsibility whatsoever for costs, losses or direct or indirect damages or costs arising from inaccuracy of information or omissions in information published on the website on behalf of BCRT.

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