We still do not know what causes most cases of rhabdomyosarcoma, but researchers have found some important clues in recent years.

Researchers are starting to understand how certain changes in DNA can cause normal cells to become cancerous. DNA is the chemical in each of our cells that makes up our genes -- the instructions for how our cells function. It is packaged in chromosomes (long strands of DNA in each cell). We normally have 23 pairs of chromosomes in each cell (one set of chromosomes comes from each parent). We usually look like our parents because they are the source of our DNA. However, DNA affects more than how we look.

Some genes are instructions for controlling when our cells grow, divide into new cells, and die. Certain genes that speed up cell division are called oncogenes. Others that slow down cell division, or cause cells to die at the right time, are called tumor suppressor genes. Cancers can be caused by DNA mutations (changes) that "turn on" oncogenes or "turn off" tumor suppressor genes.

For example, people with Li-Fraumeni syndrome have changes in the p53 tumor suppressor gene that cause it to make a defective protein. The p53 protein normally causes cells with DNA damage to either pause and repair that damage or, if repair is not possible, to self-destruct. When p53 is not working, cells with DNA damage continue to divide, causing further defects in other genes that control cell growth and development. This may lead to cancer.

Certain genes in a cell can be activated when bits of DNA are translocated (switched from one chromosome to another) when a cell is dividing into 2 new cells. This seems to be the cause of most cases of alveolar rhabdomyosarcoma (ARMS), as well as certain other childhood cancers. In these cancers, a small piece of chromosome 2 (or, less frequently, chromosome 1) is moved (translocated) onto chromosome 13. This moves a gene called PAX3 (or PAX7 if it's chromosome 1) right next to a gene called FKHR. The PAX genes play an important role in causing cells to grow while an embryo's muscle tissue is being formed, but they usually shut down once they're no longer needed. The normal function of the FKHR gene is to activate other genes. Moving them together likely activates the PAX genes, which may be what leads to the tumor forming.

Recent research suggests that embryonal rhabdomyosarcoma (ERMS) develops in a different way. Cells of this tumor have lost a small piece of chromosome 11 that came from the mother, and it has been replaced by a second copy of that part of the chromosome from the father. This seems to cause the IGF2 gene on chromosome 11 to be overactive. The IGF2 gene codes for a protein that causes these tumor cells to grow.

There is much work still to be done to understand the causes of rhabdomyosarcoma. By learning what causes this cancer, researchers hope to find more effective ways to treat it.

Last Medical Review: 09/08/2009
Last Revised: 09/08/2009