Mutations & Mutational Testing – FAQs

/Mutations & Mutational Testing – FAQs
Mutations & Mutational Testing – FAQs 2018-07-11T12:44:16+00:00


What is a gene?

Each cell of our body contains the instructions to make new cells. The instructions are contained in genes within our DNA. Genes contain the instructions for making proteins in the body. The KIT gene contains the instructions for making the KIT protein.

What is a mutation?

When a cell divides it must make a copy of all its genes (contained in DNA) so each cell will have a copy. During this process mistakes (errors) are sometimes made. The cell will try to correct these errors but if it can’t, it will typically issue its own self-destruct order. But sometimes these errors get by and get copied into the new cell. The new cell then passes on these errors each time it divides. Over time, more errors can occur. If mutations occur in certain other (critical) genes, a tumor can result.

What is a protein?

Proteins are the building blocks of the body. They are used for many different functions in the body; different proteins for different functions.

Is KIT a mutation in the gene or the protein?

A KIT mutation is a mutation in the KIT gene. Since the KIT gene contains instructions for building the KIT protein, the protein built from these bad instructions with be defective. KIT gene mutation = Defective KIT protein.

How does a mutation(s) cause cancer?

Our bodies are made up of trillions of cells all working together. There are many different types of cells in the body, for example the cells in our brains are very different than the cells from our stomach or liver. In order for all of these different types of cells to work together, they have to communicate with each other.

Normal cells in the body grow, divide, and die according to the “rules” of the body. Cancer can occur when the normal cells in our body change enough that they no longer obey the rules by which normal cells live.

Why do drugs work against some mutations in certain genes, but not others?
The new generation of cancer drugs are designed to be as specific as possible to avoid side effects. They may target as few as two or three genes, but less efficient drugs may target more (usually with more side effects)

I am KIT positive. Does that mean I have a KIT mutation?

No, this usually is referring to a stain (marker), not a mutation. It means that the KIT protein is present on the tumor cell, but it contains no information about whether the KIT protein has a mutation or not. Tumors are stained for markers to help identify the type of cancer that a patient has. KIT is one of the markers used to identify GIST. This staining/marker identification process occurs very early in the diagnosis process and is included in a pathology report, but a mutational test is a different test that is more specialized.

I have a wildtype mutation. What does that mean?

Wildtype GIST is a term that we would like to see disappear and a wildtype mutation is a nonsensical term. Wildtype actually means that the gene in question is normal, so a wildtype mutation would literally be a “normal” mutation (nonsense). It was originally used to indicate that the KIT gene was normal and starting in 2003 (when PDGFRA mutations were discovered), the term wildtype GIST meant that a patient was tested for both KIT and PDGFRA mutations and none were found, thus, KIT and PDGFRA were wildtype or normal. This is sometimes abbreviated as KIT/PDGFRA WT (wildtype). Unfortunately, mutational testing often stops at this phase and the underlying driver mutation remains undetected. This is a huge problem today. Further testing could discover the driver mutation but is seldom done. This needs to be corrected.

Mutational testing

What’s the difference between a pathology report and a mutational test?

A pathology report is an early basic test typically performed by a local pathologist at a local hospital. It is used to determine what type of cancer a patient has. It will include things like the primary tumor size, mitotic rate and primary tumor location. In GIST this information is used to help establish the risk status of a patient.
A mutational test is different from a pathology report. This should be a follow-up test, performed after a patient receives a GIST diagnosis. This test is not usually available locally but will need to be done at a specialty center. This test tells the patient which gene is mutated and which treatments will be effective or which will be ineffective.

How do you get a mutational test?

A doctor must order a mutational test. Tumor tissue, probably from your original surgery or biopsy, will be sent to a specialized lab for testing. A standard mutational test for GIST will test for mutations in the KIT gene (exons 8, 9, 11, 13 and 17) and the PDGFRA gene (exons 12, 14 and 18). This test will identify mutations in about 85% of GIST patients and no further testing is required.

If no mutation is found in KIT or PDGFRA, then further testing is necessary. This could start with a stain (marker) of the SDHB protein. A negative SDHB stain will identify all known SDH-deficient GISTs. Further testing might include other genes, including the SDH family of genes (6 genes in total), NF1, BRAF, NTRK fusions and possible others. This list includes those genes considered most likely or most actionable at this time (date of comment, 2018).

My mutational test came back as no mutations in KIT or PDGFRA. What does that mean? Do I need further testing?

Yes, the driver mutation can be determined in the vast majority of this type of GIST. Some of these driver mutations can be effectively targeted with drugs that are used to treat other cancers (such as BRAF mutations) and others can be targeted with drugs that are in trials, such as NTRK fusion mutations. In addition, the large SDH-deficient group that falls into this category has special monitoring requirements. Both SDH-deficient and NF1 type GIST have some potential concern of a familial pattern.

The mutational testing required for KIT/PDGFRA WT patients is more advanced but is obtainable. Consultation with a GIST expert may be required, although many local oncologists are also capable of arranging this type testing.

What is the cost?

The typical cost for a mutational test covering the KIT/PDGFRA genes is about $1000 in the USA, however prices may vary. Additional testing costs may vary significantly.

Will insurance pay for mutational testing?

Yes, insurance will typically pay for mutational testing. It is a test that is recommended by the NCCN (USA) as well as ESMO (Europe). Insurance coverage for more advanced testing (beyond KIT and PDGFRA) may be more difficult to get approved, but we believe that it is obtainable in most cases.

I am currently on adjuvant treatment and responding – do I still need a test?

Yes. It’s not always possible to tell if a patient is responding on adjuvant treatment since, by definition, there is no tumor to monitor after surgery. Some tumors, such as tumors with the D842V mutation seem to recur less frequently than others. This particular mutation is both lower risk and not responsive to imatinib. So, you could be taking a drug that is not going to work for a tumor that is less likely to recur. Your response of not having a tumor recur (at this time) may just be the natural course of the disease and not related to taking medication.

On the other hand, adjuvant imatinib for high-risk GIST patients with a responsive mutation type appears to be very effective and significantly improves survival, so it would be very reassuring to a patient to make sure that, if they are taking adjuvant imatinib, that they actually have a responsive mutation type.

I am currently on Gleevec for metastatic GIST and since I am responding, my doctor said I don’t need the test. Is this true?

Not in our opinion. About 80% of GIST patients on imatinib for advanced GIST will eventually progress. When that occurs, the information is likely to be useful. In addition, certain mutations, such as a KIT exon 9 mutation, should be treated with a higher dose of imatinib (as long as the higher dose is tolerated).

If you have any questions, please contact our Patient Registry Director, Denisse Montoya directly at  or call 973-837-9092 ext. 133.

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