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Read: GI stromal tumors ‘a model for what’s coming

GIST Mutation Testing

Answers to Frequently Asked Questions

1. What can I learn from having my tumor tested for mutations?
All cancers are related to DNA mutations. In approximately 80% of GISTs, mutations in the KIT gene contribute to the growth of the tumor cells. Among tumors that lack a KIT mutation, some have mutations in a closely related gene called PDGFRA (about 5-7% of all GISTs). Knowledge of the exact type and location of a mutation in the KIT or PDGFRA gene can be used to predict the likelihood that the tumor will respond to treatment with imatinib (Gleevec).

2. What is an “exon”?
If you consider a gene to be like a book, then an exon is like a chapter in the book. It is a discrete segment of the gene. When the text of an exon is altered by a mutation, it changes the meaning of the chapter – and hence that of the whole book. The altered exon corrupts the gene’s message such that it now serves to support the growth of tumor cells.

3. What mutations occur in the KIT gene, and what are their implications?
Exon 11 mutations are the most common (67% of GISTs) type and are associated with the best responses to imatinib.

Exon 9 mutations are the second most common (10% of GISTs). There is evidence that tumors with these mutations respond better when treated with high dose (800 mg/day) imatinib as opposed to standard dose (400 mg/day).

Exon 13 and exon 17 mutations are quite rare, but tumors with these mutations do respond well to imatinib.

4. What mutations occur in the PDGFRA gene, and what are their implications?
Exon 12 mutations are rare, but tumors with these mutations do respond well to imatinib.

Exon 18 mutations are a mixed group. Some are sensitive to imatinib, but the most common (4-5% of all GISTs) mutation, called “D842V” is resistant to imatinib. Patients whose tumor has this particular mutation should seek treatment with another drug, perhaps through a clinical trial.

5. What is a ‘wild-type GIST’?
Approximately 10-15% of GISTs do not have a mutation in either the KIT or PDGFRA gene. These tumors are called ‘wild-type’ in reference to the fact that their DNA is not altered in these genes. Wild-type GISTs respond to imatinib as well, or perhaps somewhat better, than GISTs with KIT exon 9 mutations, but not quite as well as GISTs with KIT exon 11 mutations.

6. Is mutation testing always necessary?
No. For many patients, surgery is all that is needed to treat their GIST. For patients whose tumor cannot be safely or completely removed by surgery, imatinib is the next choice. Decisions about the use and dose of imatinib may be influenced by mutation testing, but it is not always performed. This is in part because the response of a GIST to imatinib treatment can be readily followed by CT and/or PET scans.

7. What is needed for mutation testing?
Tumor tissue that is removed from patients, either by biopsy or surgery, is routinely processed in the hospital laboratory and embedded into wax (a so-called “paraffin block”). Some of this embedded tissue is used to make the diagnosis of GIST at the microscope, but whatever tissue is leftover is stored for at least 5 years (usually longer) in the laboratory’s archive. This material is perfectly suitable for mutation testing and can be retrieved for this purpose at any time – even years after the tissue was first obtained.

8. Is mutation testing helpful if my tumor is resistant to imatinib?
Mutation testing of tumors that show resistance to imatinib is being explored in a number of ongoing research studies, but it has not yet been adopted into routine clinical practice. In future years it is possible that such testing will play a role in the selection of other drugs used to treat imatinib-resistant tumors.

9. Is mutation testing helpful if I am taking sunitinib?
Sunitinib is generally prescribed to patients whose tumors are resistant to imatinib. At this time, mutation testing of such tumors is not part of routine practice.

10. Where can I get my tumor tested?
A number of laboratories in the U.S., Canada, Europe, Australia and Japan are offering KIT mutation testing. Testing for PDGFRA mutations is not yet widely available, but is being adopted in some of the laboratories.

The following laboratories in the U.S. have considerable experience in analyzing GISTs.
a. ARUP Laboratory, Salt Lake City (
b. MD Anderson Cancer Center, Houston, TX (
c. Oregon Health & Science University, Portland, OR (

11. Will insurance cover the cost of testing?
Mutation testing of GISTs is relatively new and there is little information available on which insurance plans will cover the costs. Because the testing is not yet standardized, charges for it vary from one laboratory to another. The charges may also be influenced by whether a tumor has a common mutation (e.g. KIT exon 11), or no mutation – requiring that all of the exons be screened.

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