What it is & what causes it?

What is Ewing’s sarcoma?

Ewing sarcoma is a type of primary bone cancer. Primary bone cancers start in the bone rather than cancer that has spread to the bone from somewhere else in the body. Ewing sarcoma is usually diagnosed in children, teenagers and young adults which corresponds with peak growth periods. Ewing sarcoma is extremely rare with only an average of 56 new cases diagnosed each year in the UK.

Most Ewing sarcoma tumours arise within the legs, pelvis and ribs. Less commonly, Ewing sarcoma can arise in other bones such as those in the arms, shoulder blades, spine, chest bone, skull and collarbone. Approximately 25% of cases at diagnosis have spread to other parts of the body (metastatic).  More rarely, Ewing sarcoma can develop in the soft tissues that support and protect the body’s organs (termed “soft tissue Ewing sarcoma”).

The most common symptoms of Ewing sarcoma are pain and swelling at the tumour site that are becoming progressively worse. These symptoms are sometimes attributed to other causes such as injuries. A key and distinctive feature of Ewing sarcoma is that the pain is worse at night, but this is not always the case. The pain may be so bad that it is difficult to fall asleep. Less frequently, symptoms can include fever, weight loss, night sweats and tiredness.

a type of primary bone cancer

Primary bone cancers start in the bone.

Mostly within the legs, pelvis & ribs

Other areas include arms, shoulder blades, spine, chest bone, skull and collarbone.

Symptoms include pain & swelling

Distinctively, the pain can be worse at night.

What causes Ewing’s sarcoma?

The causes of Ewing sarcoma are not fully understood, so we do not know how to prevent it from happening.

It is accepted in the scientific and medical community that Ewing sarcoma is somehow associated with the rapid growth of bones during development and puberty.  Genetic factors can be present in a small proportion of young people diagnosed with Ewing sarcoma. There does not appear to be any environmental factors that cause Ewing sarcoma.

There are currently no known risk factors for developing Ewing sarcoma, so it is not something anyone can prevent happening. It does occur more frequently in Caucasian males and is extremely rare in those of African or Asian descent.

Ewing sarcoma is characterised by a specific genetic fault described below, but it is unknown what causes this genetic fault. With the  progress  in genetic sequencing in large bone tumour centres, it is likely more will be known about the biology and cause for Ewing sarcoma in the future.

Humans are made up of around 37 trillion cells. In most cells there is an exact copy of the DNA molecule, which contains 20,442 protein coding genes and 23,982 non-coding genes. Protein coding genes are the set of instructions used by a cell to produce proteins. Each protein is unique and has a specific role to perform, for example, causing a single cell to divide into two cells or as a hormone that determines our mood. Non-coding genes support protein coding genes by helping to regulate how active they are, or by instructing them to switch off. 

Because DNA is a huge molecule inside our cells (albeit microscopic to the eye), it is tightly wound and packaged into complex structures called chromosomes. There are 46 chromosomes in most human cells – 23 inherited from each parent to make you. The last pair of chromosomes, known as X and Y, are the sex chromosomes. Males have one X and one Y. Females have two X’s.

In  circa 90% of Ewing sarcoma patients, a single gene on chromosome 22 called EWSR1 breaks off and joins another single gene on chromosome 11 called FLI1. This genetic event creates a “fusion gene”, which instructs a cell to make an abnormal protein. The diagram below shows pairs of chromosomes in a human cell with the most common fault observed in Ewing sarcoma patients (the EWSR1-FLI1 fusion gene). 

What causes Ewing’s sarcoma?

Individually, EWSR1 and FLI1 are normal genes that produce normal proteins that we need for our cells to function properly. However, when fused together as EWSR1-FLI1 the resultant abnormal protein causes cells to divide rapidly and form tumours. Detection of EWSR1-FLI1 in tumour specimens helps doctors to accurately diagnose Ewing sarcoma. EWSR1 can break off and fuse with other genes on other chromosomes causing Ewing sarcoma, but these cases are much rarer ( circa10%).