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GIST, gastrointestinal stromal tumors.
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Your specific mutation matters in getting the right treatment for your type of GIST.

Genetic mutations, or abnormal changes in genes, can cause cancer by making cells in the body grow and spread when they are not supposed to. In GIST, genetic mutations lead tumors to develop along with the normal cells of the gastrointestinal tract.

most common genes mutated in GIST

BRAF, B-Raf proto-oncogene, serine/threonine kinase; KIT, KIT proto-oncogene receptor tyrosine kinase; KRAS, KRAS proto-oncogene, GTPase; NF1, neurofibromin 1; PDGFRA, platelet-derived growth factor receptor alpha; SDH, succinate dehydrogenase.

aSDH deficiency refers to a decrease in succinate dehydrogenase (SUX-sin-ate dee-high-DRAW-jen-ase), a protein. The decrease can develop from mutations in specific genes.

mutated genes sometimes found in GIST
1 2 3 4 5
In the United States, 3 of 5 people with GIST may not be tested for mutations.

Reference: Bartholomew AJ, Dohnalek H, Prins PA, et al. Underuse of exon mutational analysis for gastrointestinal stromal tumors [abstract]. J Surg Res. 2018;231:43-48. doi:10.1016/j.jss.2018.05.014


Mutational testing is the only way to confirm which mutation is causing your GIST.

Confirming your specific mutation through mutational testing is the best way to ensure that your treatment plan is right for your type of GIST.

How is mutational testing done?

A sample of your tumor tissue is tested to learn which mutations are driving your GIST. The tissue needed for the test might already be available if you have had surgery for GIST. Tumor tissue is stored for several years after surgery so that taking another sample usually should not be necessary.

Testing can be done in several ways.

  • Sequencing (screening) for KIT and PDGFRA: This type of test focuses on identifying the most common GIST mutations in the KIT and PDGFRA genes. This is a common type of mutational testing in GIST.
  • Next-generation sequencing, NGS: NGS is a type of broad test that checks for many different types of general cancer mutations, including those in KIT and PDGFRA. NGS may be more expensive and results may take longer, but it provides the most information. NGS is commonly used if no mutations are detected in KIT or PDGFRA.
  • Taking a sample of circulating tumor DNA, also called a "liquid biopsy": Unlike the others, this type of test uses a blood sample. It can identify cancer mutations in DNA that “shed” from the tumor into the bloodstream by using next-generation sequencing. This type of test can provide a complete picture when GIST has several mutations (which can happen when patients have received several tyrosine kinase inhibitor [TKI] medicines to treat their cancer). The technology needs to be studied further before it is used routinely in GIST care.

What is immunohistochemistry, or IHC staining, for KIT?

This type of test helps your doctor determine whether the tissue removed (or resected) is GIST or something else. It may lead to a report that says your GIST tests positive for KIT, but it is not the same as mutational testing. It cannot confirm if you have a KIT mutation.

Results of the test are usually available in 2 weeks, although it can take longer.

Ask your care team when you will get your results. They may recommend that you start a treatment before you receive them.

The test results will tell you about your mutation.
Think of the results like an address:

the gene is the city gene map
the exon is the street exon map
the alteration is the house number alteration map

Example results of GIST mutational testing

Gene Exon Alteration
KIT exon 11 V559D
PDGFRA exon 18 D842V
 

Some test results may not include your exon, but results should always include information about your gene and alteration. The alteration listed in mutational test results can represent a change in the amino acid or DNA change. Ask your doctor to explain what this means for you.

know the gene and alteration that are driving your GIST
Without knowing the gene and alteration that are driving your GIST, you may be starting treatment with incomplete information.

Expert treatment guidelines for GIST recommend mutational testing for all patients.

Listen to a GIST expert explain why it is important for people with GIST to know which mutation they have.

Knowing the type of mutation you have will help your doctor find the right treatment for your GIST.

Testing as soon as possible is best. This improves your chances of avoiding treatments that don’t work and starting one that is most likely to help. The results of mutational testing may give your doctor answers to these questions:

It’s important to consult with an expert on GIST to understand all treatment options for your mutation.

GIST is a rare and complex type of cancer. Your treatment should be the right one for the exact mutation causing it. The first treatment (called first-line treatment) for most patients who have advanced GIST is the drug imatinib.

  • The normal indicated dose of imatinib is 400 milligrams per day.
  • Patients with some mutations may need a higher dose of imatinib or a different medicine altogether.
  • Some mutations can prevent imatinib from working at all.
Did you know?
For up to 30% of GIST mutations, imatinib may not work, or a higher dose may be recommended.

Reference: Bannon AE, Klug LR, Corless CL, Heinrich MC. Using molecular diagnostic testing to personalize the treatment of patients with gastrointestinal stromal tumors. Expert Rev Mol Diagn. 2017;17(5):445-457.

New treatments for GIST are being developed. It may be possible for patients to get them by being part of a clinical trial. Talk with your doctor to learn if you are able to join a clinical trial for your GIST.

To find a GIST specialist, visit

http://liferaftgroup.org/gist-specialists.

Suggested resources for patients living with GIST

Blueprint Medicines and patient advocacy organizations are committed to increasing mutational testing in GIST. Find more information about GIST from experts, as well as support for patients and caregivers, at the following websites:

The Life Raft Group

GIST Support International

Sarcoma Patients EuroNet

Download and print the My Mutation Matters discussion guide to help you discuss mutational testing with your care team.
My Mutation Matters discussion guide
Download

Frequently asked questions

References

  • Bannon AE, Klug LR, Corless CL, Heinrich MC. Using molecular diagnostic testing to personalize the treatment of patients with gastrointestinal stromal tumors. Expert Rev Mol Diagn. 2017;17(5):445-457.
  • Bartholomew AJ, Dohnalek H, Prins PA, et al. Underuse of exon mutational analysis for gastrointestinal stromal tumors [abstract]. J Surg Res. 2018;231:43-48. doi:10.1016/j.jss.2018.05.014
  • Casali PG, Abecassis N, Bauer S, et al, on behalf of the ESMO guidelines Committee and EURACAN. Gastrointestinal stromal tumours: ESMO–EURACAN Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2018;29(suppl 4):iv68-iv78. Retrieved November 27, 2018, from the European Society for Medical Oncology website.
  • Corless C. How ‘Next Generation’ DNA sequencing is changing the landscape of GIST research and diagnosis. Life Raft Group website. https://liferaftgroup.org/2013/06/how-next-generation-dna-sequencing-is-changing-the-landscape-of-gist-research-and-diagnosis. Published June 11, 2013. Accessed January 2, 2019.
  • Corless CL, Schroeder A, Griffith D, et al. PDGFRA mutations in gastrointestinal stromal tumors: frequency, spectrum and in vitro sensitivity to imatinib. J Clin Oncol. 2005;23(23):5357-5364.
  • Demetri GD, Benjamin RS, Blanke CD, et al. NCCN Task Force report: management of patients with gastrointestinal stromal tumor (GIST)—update of the NCCN clinical practice guidelines. J Natl Compr Cancer Network. 2007;5(2_suppl):S-1-S-31.
  • Finding good care. GIST Support International website. http://www.gistsupport.org/about-gist/for-new-gist-pages/finding-good-care. Published October 18, 2010. Accessed January 2, 2019.
  • Gastrointestinal stromal tumor. Genetics Home Reference. National Institutes of Health website. https://ghr.nlm.nih.gov/condition/gastrointestinal-stromal-tumor. Updated January 2, 2019. Accessed January 2, 2019.
  • Gastrointestinal stromal tumor - GIST: about clinical trials. American Society of Clinical Oncology website. https://www.cancer.net/cancer-types/gastrointestinal-stromal-tumor-gist/about-clinical-trials. Published October 17, 2018. Accessed January 2, 2019.
  • GIST diagnosis. Life Raft Group website. https://liferaftgroup.org/gist-diagnosis. Accessed January 2, 2019.
  • Gleevec [package insert]. East Hanover, NJ: Novartis Pharmaceuticals Corporation; 2018.
  • Hameed M, Corless C, George S, et al, for the Members of the Cancer Biomarker Reporting Committee, College of American Pathologists. Template for reporting results of biomarker testing of specimens from patients with gastrointestinal stromal tumors [published online for public access]. Arch Pathol Lab Med. 2015;139(10):1271-1275. doi:10.5858/arpa.2014-0578-CP
  • Knowing your mutation and mutational testing. Life Raft Group website. https://liferaftgroup.org/mutations-in-gist. Accessed January 2, 2019.
  • Lee J-H, Kim Y, Choi J-W, Kim Y-S. Correlation of imatinib resistance with the mutational status of KIT and PDGFRA genes in gastrointestinal stromal tumors: a meta-analysis. J Gastrointestin Liver Dis. 2013;22(4):413-418.
  • Miettinen M, Lasota J. Gastrointestinal stromal tumors [published online for public access]. Gastroenterol Clin North Am. 2013;42(2):399-415. doi:10.1016/j.gtc.2013.01.001
  • Mutation testing. GIST Support International website. http://www.gistsupport.org/about-gist/for-new-gist-pages/mutation-testing. Accessed November 26, 2018.
  • Nassar A. Biopsy: 5 things every patient should know. American Society of Clinical Oncology website. https://www.cancer.net/blog/2016-05/biopsy-5-things-every-patient-should-know. Published May 31, 2016. Accessed January 2, 2019.
  • Nishida T, Blay J-Y, Hirota S, Kitagawa Y, Kang Y-K. The standard diagnosis, treatment, and follow-up of gastrointestinal stromal tumors based on guidelines. Gastric Cancer. 2016;19(1):3-14.
  • Owens B. Mutational testing and genetics. Life Raft Group website. https://liferaftgroup.org/2018/08/mutational-testing-and-genetics. Published August 15, 2018. Accessed January 2, 2019.
  • Poveda A, del Muro XG, López‑Guerrero JA, et al. GEIS 2013 guidelines for gastrointestinal sarcomas (GIST) [published online for public access]. Cancer Chemother Pharmacol. 2014;74(5):883-898. doi:10.1007/s00280-014-2547-0
  • Schwaederle M, Husain H, Fanta PT, et al. Use of liquid biopsies in clinical oncology: pilot experience in 168 patients. Clin Cancer Res. 2016;22(22):5497-5505.
  • Shi E, Chmielecki J, Tang C-M, et al. FGFR1 and NTRK3 actionable alterations in “wild‑type” gastrointestinal stromal tumors [published online for public access]. J Transl Med. 2016;14(1):339. doi:10.1186/s12967-016-1075-6
  • Solid tumors GeneTrails GIST genotyping panel. Oregon Health & Science University website. https://knightdxlabs.ohsu.edu/home/test-details?id=GeneTrails+GIST+Genotyping+Panel. Accessed January 2, 2019.
  • Søreide K, Sandvik OM, Søreide JA, Giljaca V, Jureckova A, Bulusu VR. Global epidemiology of gastrointestinal stromal tumours (GIST): a systematic review of population-based cohort studies [published online for public access]. Cancer Epidemiol. 2016;40:39-46. doi:10.1016/j.canep.2015
  • Szucs Z, Thway K, Fisher C, et al. Molecular subtypes of gastrointestinal stromal tumors and their prognostic and therapeutic implications. Future Oncol. 2017;13(1):93-107.
  • Tests for gastrointestinal stromal tumors. American Cancer Society website. https://www.cancer.org/cancer/gastrointestinal-stromal-tumor/detection-diagnosis-staging/how-diagnosed.html. Updated May 17, 2017. Accessed January 25, 2019.
  • Understanding GIST. Life Raft Group website. https://liferaftgroup.org/understanding-gist. Accessed January 2, 2019.
  • Wardelmann E, Merkelbach-Bruse S, Pauls K, et al. Polyclonal evolution of multiple secondary KIT mutations in gastrointestinal stromal tumors under treatment with imatinib mesylate. Clin Cancer Res. 2006;12(6):1743-1749.
  • What is a clinical trial. Life Raft Group website. https://gisttrials.org/iLRG/clinical-trial-overview.html. Accessed January 2, 2019.
  • What is circulating tumor DNA and how is it used to diagnose and manage cancer? Help me understand genetics. Genetics Home Reference. National Institutes of Health website. https://ghr.nlm.nih.gov/primer/testing/circulatingtumordna. Published January 2, 2019. Accessed January 2, 2019.
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