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Causes, Risk Factors, and Prevention TOPICS

Do we know what causes rhabdomyosarcoma?

Researchers still do not know what causes most cases of rhabdomyosarcoma (RMS), but they are learning 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. But DNA affects more than how we look.

Some genes control when our cells grow, divide into new cells, and die. Certain genes that help cells grow, divide, or stay alive are called oncogenes. Others that slow down cell division or make cells die at the right time are called tumor suppressor genes. Cancers can be caused by DNA changes that turn on oncogenes or turn off tumor suppressor genes.

For example, people with Li-Fraumeni syndrome have changes in the TP53 tumor suppressor gene that cause it to make a defective p53 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 turned on when bits of DNA are switched from one chromosome to another. This type of change, called a translocation, can happen when a cell is dividing into 2 new cells. This seems to be the cause of most cases of alveolar rhabdomyosarcoma (ARMS). In these cancers, a small piece of chromosome 2 (or, less often, chromosome 1) ends up on chromosome 13. This moves a gene called PAX3 (or PAX7 if it’s chromosome 1) right next to a gene called FOXO1. The PAX genes play an important role in causing cells to grow while an embryo’s muscle tissue is being formed, but these genes usually shut down once they’re no longer needed. The normal function of the FOXO1 gene is to activate other genes. Moving them together probably activates the PAX genes, which may be what leads to the tumor forming.

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 may make these tumor cells grow. Other gene changes are probably important in these tumors as well.

Changes in several different genes are usually needed for normal cells to become cancer cells. Scientists have found other gene changes that set some RMS cells apart from normal cells, but there are likely others that have not yet been found.

Researchers now understand many of the gene changes that can lead to RMS, but it’s still not clear what might cause these changes. Some gene changes may be inherited. Others might just be a random event that sometimes happens inside a cell, without having an outside cause. There are no known lifestyle-related or environmental causes of RMS, so it is important to know that there is nothing these children or their parents could have done to prevent these cancers.

Last Medical Review: 08/13/2013
Last Revised: 08/13/2013