In a recently published article in Nature Genetics, several prominent cancer researchers and GIST experts, led by Dr. Dr. Yuexiang Wang and including Dr. Jonathan Fletcher of Brigham & Women’s Hospital and Dr. Matthew van de Rijn of Stanford University Center, who are both members of the LRG’s research team, discuss new research findings that may potentially help identify GIST patients with a future high risk for metastases.
Lack of dystrophin expression is a key factor in the development of muscular dystrophy. Muscular dystrophy (MD) is the name given to a group of disorders which cause muscle weakness. There are many different types of MD. The different types vary as to how mild or severe they are, and which muscles they affect. The cause is an abnormal or “faulty” gene. Genes are made from a biological material called DNA. Genes are the “control center” of each cell in the body, including muscle cells. The genes control the proteins that the cell makes. Certain genes control the proteins for muscle fibers to work properly. It is these genes that are involved in MD.
The “faulty” gene in MD means that one of the proteins needed by muscle cells (Dystrophin) cannot be made correctly. This leads to damaged muscle fibers and to muscle weakness. Depending on the exact type of faulty gene and faulty protein, different types of muscle weakness result. This is why there are different types of MD.
Within the muscular dystrophy associated DMD gene, intragenic deletion of dystrophin is a frequent mechanism by which myogenic tumors progress to lethal sarcomas. Dystrophin inhibits myogenic sarcoma cell migration and invasion, acting as a tumor suppressor.
Dystrophin inactivation was found in 96 percent of metastatic GIST cases in the study. This is a significant finding that impacts the direction of future research studies.The implication is that by detecting key genetic defects such as the lack of dystrophin in GIST patients, that it may eventually be possible to predict those who will develop metastatic disease. It may eventually lead to targeted therapies for both diseases.
According to Dr. Fletcher:
“Inherited inactivation of dystrophin causes the most common and severe form of muscular dystrophy (Duchenne Muscular Dystrophy). In this paper, Dr. Yuexiang Wang and colleagues show that mutational inactivation of dystrophin causes progression and metastasis in GIST. These advances provide a rationale for evaluating various therapies under development for muscular dystrophy as new therapeutic strategies for GIST. Indeed, we hope the research juxtapositions of GIST vs. muscular dystrophy will create opportunities for both fields. One very appealing aspect is that drugs going forward as potential chronic therapies for youngsters with severe muscular dystrophy….have to be well-tolerated.“
As a rare disease, GIST does not garner the attention, both from the research community, and from the general public, that diseases with a larger number of patients do.
On the other hand, muscular dystrophy has a significantly higher level of public awareness. Since both diseases share these genetic commonalities, the opportunities for collaborative research studies are promising.
To read the article, click here.