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EZH2 Mutation Analysis Test

Last updated Feb. 1, 2017

Approved by: Krish Tangella MD, MBA, FCAP

The EZH2 Mutation Analysis Test is a genetic test to detect abnormalities in the EZH2 gene. It is used to diagnose lymphoma. It also aids in the treatment of lymphoma by guiding selection of therapeutic drugs, including disqualifying certain drugs from use.

What are other Names for this Test? (Equivalent Terms)

  • Enhancer of Zeste Homolog 2 Mutation Analysis Test

What is EZH2 Mutation Analysis Test? (Background Information)

  • EZH2 mutation refers to an alteration in the EZH2 gene. It is associated with cancer of the lymphatic cells, called lymphoma. The lymphatic cells are the body’s specialized immune system cells
  • The EZH2 gene gives instructions for the EZH2 protein; EZH2 refers to enhancer of zeste homolog 2. The EZH2 protein helps regulate the development of a growing embryo by controlling how its genes are turned into proteins
  • EZH2 performs its gene regulating function by attaching chemical groups to DNA through a process called methylation. Methylated DNA is essentially turned off. EZH2 ‘methylates’ DNA in many regions, which makes it very important for proper embryonic development
  • An abnormal EZH2 gene may result in a faulty EZH2 protein that is always turned on. Consequently, EZH2 excessively turns off genes that are important for preventing the development of cancer, such as tumor suppressing genes
  • Lymphocytes, specialized cells of the immune system, are especially susceptible to mutations in the EZH2 gene. They are prone to turning cancerous in the presence of such mutations, and thus, lymphoma is the most common result of EZH2 mutation
  • The EZH2 Mutation Analysis Test is a genetic test to detect abnormalities in the EZH2 gene. It is used to diagnose lymphoma. It also aids in the treatment of lymphoma by guiding selection of therapeutic drugs, including disqualifying certain drugs from use

The molecular testing, in general, can be performed using a variety of methods. Some of these methods include:

  • In situ hybridization technique, such as fluorescence in situ hybridization (FISH)
  • Immunohistochemistry (IHC)
  • Next-generation sequencing (NGS)
  • Polymerase chain reaction (PCR)
  • Comparative genomic hybridization (CGH)
  • Karyotyping including spectral karyotyping
  • mRNA analysis
  • Tissue microarrays (TMAs)
  • Southern blot test
  • Northern blot test
  • Western blot test
  • Eastern blot test

The methodology used for the test may vary from one laboratory to another. 

Note: Molecular testing has limitations due to the molecular method and genetic mutational abnormalities being tested. This can affect the results on a case-by-case basis. Consultation with your healthcare provider will help in determining the right test and right molecular method, based on individual circumstances.

What are the Clinical Indications for performing the EZH2 Mutation Analysis Test?

Following are the clinical indications for performing the EZH2 Mutation Analysis Test: 

  • Painless swelling of the lymph nodes of the neck, armpit, and/or groin
  • Fatigue
  • Rapid and unexplained weight loss
  • Night sweats, fever

In general, the molecular genetic testing is undertaken in the following situations: 

  • To assist (and in some cases, confirm) the initial diagnosis
  • To distinguish other tumors/conditions that have similar histological features, when examined by a pathologist under the microscope
  • To help in determining treatment options
  • To confirm recurrence of the tumor: Tumor recurrence can either be at the original tumor site, or at a distant location (away from the initial site)

How is the Specimen Collected for the EZH2 Mutation Analysis Test?

Following is the specimen collection process for EZH2 Mutation Analysis Test:

The specimen sample requirements may vary from lab to lab. Hence, it is important to contact the testing lab for exact specimen requirements, before initiating the testing process.

  • Sample on which the test is performed may include:
    • Fresh tumor tissue during biopsy
    • Formalin-fixed paraffin-embedded solid tumor tissue (FFPE tumor tissue), often referred to as paraffin block of the tumor
    • Unstained tissue slides
  • Process of obtaining the sample: As outlined by the laboratory testing facility
  • Preparation required: As outlined by the laboratory testing facility


  • In some cases, a different source of specimen (such as peripheral blood, bone marrow biopsy specimen, or other body fluids) may be acceptable to the laboratory performing the test
  • Occasionally, additional samples may be required to either repeat the test or to perform follow-up testing
  • Depending on the location of testing, it may take up to 2 weeks’ turnaround time, to obtain the test results
  • Many hospitals preserve the paraffin blocks for at least 7 years. In general, older paraffin blocks (over 5 years) may affect the detection of specific mutations, due to degradation of the tumor specimen over time

Cost of EZH2 Mutation Analysis Test:

  • The cost of the test procedure depends on a variety of factors, such as the type of your health insurance, annual deductibles, co-pay requirements, out-of-network and in-network of your healthcare providers and healthcare facilities
  • In many cases, an estimate may be provided before the test is conducted. The final amount may depend upon the findings during the test procedure and post-operative care that is necessary (if any)

What is the Significance of the EZH2 Mutation Analysis Test Result?

A mutation in the EZH2 gene indicates a positive result for the EZH2 Mutation Analysis Test. This may point to a diagnosis of:

  • Follicular lymphoma
  • Germinal center B-cell type diffuse large B-cell lymphoma

The laboratory test results are NOT to be interpreted as results of a "stand-alone" test. The test results have to be interpreted after correlating with suitable clinical findings and additional supplemental tests/information. Your healthcare providers will explain the meaning of your tests results, based on the overall clinical scenario.

Additional and Relevant Useful Information:

  • EZH2 gene mutations are linked with 27% of cases of follicular lymphoma, a type of non-Hodgkin lymphoma
  • Many laboratories may not have the capability to perform this test. Only highly-specialized labs with advanced facilities and testing procedures may perform this test

Certain medications that you may be currently taking may influence the outcome of the test. Hence, it is important to inform your healthcare provider of the complete list of medications (including any herbal supplements) you are currently taking. This will help the healthcare provider interpret your test results more accurately and avoid unnecessary chances of a misdiagnosis.

What are some Useful Resources for Additional Information?

The following DoveMed website link is a useful resource for additional information:


Please visit our Laboratory Procedures Center for more physician-approved health information:


References and Information Sources used for the Article:

https://ghr.nlm.nih.gov/primer/testing/genetictesting (accessed on 05/10/2017)

https://www.cdc.gov/mmwr/preview/mmwrhtml/rr5806a1.htm (accessed on 05/10/2017)

http://www.nature.com/gim/journal/v10/n5/full/gim200852a.html (accessed on 05/10/2017)

http://pediatrics.aappublications.org/content/106/6/1494 (accessed on 05/10/2017)

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Brenner, V. E., Blanchon, D. R., & Didelot, F. M. (2006). The Polycomb group protein EZH2 directly controls DNA methylation. Nature, 439(7078), 871-4. doi:10.1038/nature04431

Follicular lymphoma - Understanding - Macmillan Cancer Support. (n.d.). Retrieved from http://www.macmillan.org.uk/information-and-support/lymphoma/lymphoma-non-hodgkin/understanding-cancer/types-of-non-hodgkin-lymphoma/follicular-lymphoma.html

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Druker, B. J. Perspectives on the development of a molecularly targeted agent. Cancer Cell 1, 31–36 (2002)

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Pinkel, D., et al. High resolution analysis of DNA copy number variation using comparative genomic hybridization to microarrays. Nature Genetics 20, 207–211 (1998) doi:10.1038/2524

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Souroullas, G. P., Jeck, W. R., Parker, J. S., Simon, J. M., Liu, J. Y., Paulk, J., ... & Burd, C. E. (2016). An oncogenic Ezh2 mutation induces tumors through global redistribution of histone 3 lysine 27 trimethylation. Nature medicine, 22(6), 632-640.

Bödör, C., Grossmann, V., Popov, N., Okosun, J., O’Riain, C., Tan, K., ... & Clear, A. (2013). EZH2 mutations are frequent and represent an early event in follicular lymphoma. Blood, 122(18), 3165-3168.

Papaemmanuil, E., Gerstung, M., Malcovati, L., Tauro, S., Gundem, G., Van Loo, P., ... & Shlien, A. (2013). Clinical and biological implications of driver mutations in myelodysplastic syndromes. Blood, 122(22), 3616-3627.

Souroullas, G. P., Jeck, W. R., Parker, J. S., Simon, J. M., Liu, J. Y., Paulk, J., ... & Burd, C. E. (2016). An oncogenic Ezh2 mutation cooperates with particular genetic alterations to induce tumors in mice and redistributes H3K27 trimethylation throughout the genome.

da Cunha Santos, G., Saieg, M. A., Ko, H. M., Geddie, W. R., Boerner, S. L., Craddock, K. J., ... & Bailey, D. (2015). Multiplex sequencing for EZH2, CD79B, and MYD88 mutations using archival cytospin preparations from B‐cell non‐Hodgkin lymphoma aspirates previously tested for MYC rearrangement and IGH/BCL2 translocation. Cancer cytopathology, 123(7), 413-420.

Booth, C., Barkas, N., Neo, W. H., Soilleux, E., Boukarabila, H., Giustacchini, A., ... & Atkinson, D. (2015). Ezh2 and Runx1 Mutations Targeted to Early Lymphoid Progenitors Collaborate to Promote Early Thymic Progenitor Leukemia. Blood, 126(23), 846-846.

Reviewed and Approved by a member of the DoveMed Editorial Board
First uploaded: Feb. 1, 2017
Last updated: Feb. 1, 2017