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 how bone cells may become cancerous.

Over the last few years, there has been a lot of research into the biology of Ewing's sarcoma. However, despite this research the understanding of the biology of Ewing's sarcoma and what causes cells to become malignant in Ewing's is still moving forward quite slowly.

It is known that cells contain important information in their chromosomes called genes, which help them to divide and grow normally. Damage to these genes can cause the cell to behave differently and grow abnormally, which can then lead to development of cancer.

In Ewing's sarcoma, there is damage to the cell's genetic information such as abnormalities of the genes (mutations) or rearrangement of the chromosomes called 'translocations.'

Chromosomes and chromosome translocations

Chromosomes

In figure 1(a), you can see the chromosomes are numbered from 1 to 22, (sex chromosome X or Y is number 23). Humans have 23 pairs of chromosomes including 1 pair of sex chromosomes (XY (male) or XX (female)); we receive 23 from our mothers and 23 from our fathers.

Figure 1 (a), Diagram of Human Chromosomes (karotype).

If you look at figure 1a, the long arms of chromosomes are given the letter 'q'; the short arms are given the letter 'p.' The banding or stripes come from a stain added by a scientist to help show up different areas of the chromosome under the microscope. Each band is numbered for identification.

Chromosomes are only visible under a light microscope when the cells divide at a stage of cell division called 'metaphase' see figure 1(b). The study of these visible chromosomes is carried out by scientists known as cytogeneticists (SY-tow-geh-NET-eh-sist).

Figure 1 (b) Micrograph of Cells Showing Visible Chromosomes.

Chromosome Translocations

In Ewing's sarcomas, there is a rearrangement of the chromosomes known as a translocation.

In around 90% of Ewing's sarcomas, 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. This means 't' 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.

How do translocations cause problems in cells?

When a translocation occurs, it interferes with the genes. Genes can be lost or new ones formed by the fusion of two pre-existing genes at the point at which the translocation occurs. If the lost gene was one which was important for normal cell division or which would prevent a cell from becoming cancerous then a tumour might develop.

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

The EWS-FLI1 fusion gene instructs the cell to make EWS-FLI1 fusion protein. This protein is thought to affect further instructions in the cell by switching other genes on or off. Changes in the cell's instructions can cause cells to become malignant.

There are also other chromosomal abnormalities and genetic mutations in many Ewing's cases.

The changes in the cell's instructions in the form of chromosome translocations or other changes in the DNA such as mutations only happen in the tumour cells. They do not occur in sperm or egg cells; therefore, they cannot be passed on to 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?

Discovery of the exact cell type in which Ewing's sarcoma starts is a big area of research. This could allow scientists and doctors to work out what causes the chromosome translocations and other genetic damage as the cancer starts and progresses.

Understanding the biology of cancer cells helps doctors and scientists to look for, and find targets for treatments and markers (clues that it is Ewing's) that can help diagnosis. For example, treatments that target or inhibit the EWS-FLI1 'fusion' protein.


Last reviewed: October 2010; Version: 1.1
Review due: October 2011

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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