Two Mutations Cause Same Type of Gastrointestinal Cancer

A recent study on the causes of gastrointestinal stromal tumors (GISTs) has revealed that a defective protein coded by a mutated form of the platelet-derived growth factor receptor alpha (PDGFRA) gene is sometimes involved in the development of the disease. The finding was reported January 9, 2002, in the online edition of Science.

GISTs invade the organs or linings of the gastrointestinal tract, and being unresponsive to conventional treatments, they are usually fatal. Previously it had been reported that GISTs possessed a defective version of a distinct tyrosine kinase enzyme called KIT. The mutation caused the KIT enzyme in GIST cells to be switched on in an uncontrolled manner. This mutation accounted for about 85% of GISTs.

While searching for the cause of GIST not related to defective KIT, investigators from Oregon Health & Science University (Portland, USA) found that 14 of 40 (35%) GIST tumors lacking KIT mutations instead had mutations in the related receptor tyrosine kinase, PDGFRA. There were no detectable differences in tumor cells whether of KIT or PDGFRA origin.

Of particular interest to the researchers was the observation that GISTs of KIT origin responded well to the anticancer drug Gleevec while those derived from PDGFRA were not sensitive to the drug.

"PDGFRA is found in many body tissues, so it also will be important to determine whether mutations in this enzyme might play a role in other cancers,” said first author Dr. Michael Heinrich, associate professor of medicine at the Oregon Health & Science University Cancer Institute.



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