Genetic testing is one of the tools used to diagnose systemic mastocytosis (SM). Doctors primarily use it to look for mutations in the KIT gene that drive the uncontrolled growth and survival of mast cells.
While KIT testing is just one part of the diagnostic picture, it plays a key role in confirming a diagnosis, classifying the disease and helping guide treatment decisions.
What is the KIT gene?
The KIT gene provides instructions for producing a receptor tyrosine kinase, a protein that carries messages to cells throughout the body and helps regulate cell growth, development and survival.
In most people with SM, the KIT gene has acquired a mutation that causes the receptor to remain permanently switched on. As a result, mast cells continue to grow and multiply out of control.
The most common mutation is called KIT D816V, which is found in more than 90% of adults with SM. However, some people have other, less common KIT mutations, and a small number have no detectable KIT mutation using standard testing methods.
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Why is KIT testing important in mastocytosis?
Finding a KIT mutation, particularly KIT D816V, provides strong evidence that someone has SM.
When combined with bone marrow examination and other diagnostic criteria, it also helps determine which subtype of SM a person has. This in turn can give doctors a better idea of your prognosis and help them design a treatment plan.
On the other hand, if your have symptoms of mast cell activation but testing doesn’t find any type of KIT mutation, it can help point doctors to another diagnosis, such as mast cell activationMast cell activation Describes when mast cells release histamine and other mediators into the blood stream in response to an allergen or other trigger. This leads to symptoms like fatigue, rash and, in severe cases, anaphylaxis. syndrome.
Keep in mind that KIT testing is just one part of the diagnostic process. Doctors also consider symptoms, blood tests such as serum tryptaseTryptase A protein enzyme that is primarily produced by mast cells and stored in small pockets within the cells, known as granules. High levels of tryptase are a key indicator of SM. levels, bone marrow biopsyBone marrow biopsy A procedure to collect a sample of bone marrow using a needle. Often used to examine the characteristics of mast cells and diagnose SM. findings, imaging tests and other laboratory results. Together, all these pieces of information provide a more complete understanding of your disease.
How is genetic testing done?
KIT testing is usually performed on a blood or bone marrow sample. The sample is sent to a lab where sequencing technology is used to locate mutations.
The KIT mutation isn’t the easiest to find. The number of abnormal mast cells carrying the mutation is often low, so doctors use very sensitive tests to find them. Two of the most highly sensitive tests are:
- Allele-specific oligonucleotide quantitative PCR (ASO-qPCR).
- Droplet digital PCR (ddPCR).
Both methods are designed to detect the KIT D816V mutation even when only a very small number of abnormal mast cells are present, making them much less likely to miss the mutation than older testing techniques.
However, a negative blood test does not always rule out SM: In some patients with SM the bone marrow can test positive for the KIT mutation even though the blood does not, and other patients may have SM but no KIT mutation at all. If symptoms and other findings strongly suggest SM, a bone marrow biopsy and additional testing may still be needed.
Read more about the genetics of systemic mastocytosisMastocytosis Rare disease caused by the buildup of mast cells. Cutaneous mastocytosis primarily affects the skin and is more common in children, while systemic mastocytosis affects internal organs and is more common in adults.: “Can you inherit systemic mastocytosis?”
