What is Rhabdomyosarcoma?

We have had a few newbies join the rhabdo-list (online support group) and this question has come up. One of the supporters, James Atkinson, is particularly knowledgable and explained it as follows:

Alveolar Rhabdomyosarcoma exhibits genetic translocations either between t(2;13)(q35;q14) or t(1;13)(p36;q14).

The former generates the fusion gene PAX3 -FOX01, which account for around 60% of ARMS cases.

The latter generates the fusion gene PAX7 - FOXO1, which account for around 20% of ARMS cases.

The protein generated by these fusion genes is unique in the body and might end up providing a target for future vaccine therapies.

Embryonal Rhabdomyosarcoma does not have recurrent structural chromosome rearrangements, but rather has frequent chromosome gains and losses. In addition, ERMS has a much higher frequency of loss of one of the two alleles of many chromosome 11 loci, particularly in the 11p15.5 region.

source: http://atlasgeneticsoncology.org/Tumors/rhab5004.html

These genetic abnormalities occur in the cells themselves, presumably in immature muscle cells -- rhabdomyoblasts -- that have not yet matured into 'real' muscle cells. Under the microscope, rhabdomyosarcoma cells can resemble fetal muscle cells.

These genetic abnormalities are *not* part of the genome and cannot (so far as we know) be passed from parent to offspring. Children likely are not born with a predisposition to rhabdomyosarcoma unless they have some other genetic condition, like P53 knockout, that can lead to tumor development.
Rhabdo genetic errors very likely are just accidents.

I note in passing that the rhabdomyoblast theory does not account for adults like my wife who acquired rhabdomyosarcoma in adulthood, when presumably all rhabdomyoblasts have matured. There is a school of research that suggests that mature muscle cells can revert to immature blasts under as-yet-unknown conditions.

If researchers can figure out that precise mechanism, we should understand RMS genesis for most patients much better...and be able to craft new treatments to leverage that new understanding.

When prompted to restate in a manner that an 87-year old grandfather could understand, James posted again with:

Twitter version: Two genes get transposed in muscle cells. Bad things happen.

As I've mentioned before, alveolar rhabdo (ARMS) is more agressive than embryonal (ERMS).

And there ya go.

Lori