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ETV6 Mutation Analysis Test

Last updated Feb. 1, 2017

Approved by: Maulik P. Purohit MD MPH

The ETV6 Mutation Analysis Test is a genetic test to detect abnormalities in the ETV6 gene. It is used to diagnose leukemia.


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

  • ETS-Related Protein Tel1 Mutation Analysis Test
  • ETS Variant Gene 6 (TEL Oncogene) Mutation Analysis Test
  • Transcription Factor ETV6 Mutation Analysis Test

What is ETV6 Mutation Analysis Test? (Background Information)

  • ETV6 mutation refers to an alteration in the ETV6 gene, which is associated with white blood cell cancer (or leukemia)
  • The ETV6 gene gives instructions for the ETV6 protein. ETV6 helps control the conversion of genetic information into protein (gene expression). Specifically, ETV6 turns off the activity of certain genes required for the growth and division of white blood cells (leukocytes)
  • Mutation of the ETV6 protein results in a protein product that is a fusion of two proteins. The abnormal ETV6 is unable to turn off genes that the normal ETV6 protein is responsible for repressing. As a result, white blood cells grow unchecked
  • A class of white blood cells called eosinophils is most frequently affected by a mutation in ETV6, although the reason for this is unclear. The most common condition caused by ETV6 mutation is PDGFRB-associated chronic eosinophilic leukemia
  • The ETV6 Mutation Analysis Test is a genetic test to detect abnormalities in the ETV6 gene. It is used to diagnose leukemia. It also aids in the treatment of leukemia 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 ETV6 Mutation Analysis Test?

Following are the clinical indications for performing the ETV6 Mutation Analysis Blood Test: 

  • Fever and chills
  • Excessive sweating, especially at night
  • Persistent fatigue, weakness
  • Frequent or severe infections
  • Losing weight without trying
  • Swollen lymph nodes, enlarged liver or spleen
  • Easy bleeding or bruising
  • Recurrent nosebleeds
  • Tiny red spots on skin (petechiae)
  • Bone pain or tenderness

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 ETV6 Mutation Analysis Test?

Following is the specimen collection process for ETV6 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

Note:

  • 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 ETV6 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 ETV6 Mutation Analysis Test Result?

A mutation in the ETV6 gene indicates a positive result for the ETV6 Mutation Analysis Test. This may point to a diagnosis of:

  • PDGFRB-associated chronic eosinophilic leukemia
  • Acute myeloid leukemia (AML)
  • Acute lymphoblastic leukemia (ALL)
  • Myelodysplastic syndrome (MDS)

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:

  • ETV6 mutation most notably occurs in a location of the chromosome called 12p13.2 - i.e., the short arm (p) of chromosome 12 in position 13.2
  • 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:

http://www.dovemed.com/diseases-conditions/leukemia-and-lymphoma/

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

http://www.dovemed.com/common-procedures/procedures-laboratory/

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)

ETV6 gene - Genetics Home Reference. (n.d.). Retrieved from https://ghr.nlm.nih.gov/gene/ETV6#location

Mayo Clinic. (2016, January 28). Leukemia Symptoms. Retrieved from http://www.mayoclinic.org/diseases-conditions/leukemia/basics/symptoms/con-20024914

Zhang, M. Y., Churpek, J. E., & Keel, S. B. (2015). Germline ETV6 mutations in familial thrombocytopenia and hematologic malignancy. Nature Genetics, 47, 180-5. doi:10.1038/ng.3177

Helpful Peer-Reviewed Medical Articles:

Carrano, A. V., et al. Measurement and purification of human chromosomes by flow cytometry and sorting. Proceedings of the National Academy of Sciences 76, 1382–1384 (1979)

Drets, M. E., & Shaw, M. W. Specific banding patterns of human chromosomes. Proceedings of the National Academy of Sciences 68, 2073–2077 (1971)

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

Parra, I., & Windle, B. High resolution visual mapping of stretched DNA by fluorescent hybridization. Nature Genetics 5, 17–21 (1993) doi:10.1038/ng0993-17

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

Speicher, M. R., et al. Karyotyping human chromosomes by combinatorial multi-fluor FISH. Nature Genetics 12, 368–375 (1996) doi:10.1038/ng0496-368

Zhang, M. Y., Churpek, J. E., Keel, S. B., Walsh, T., Lee, M. K., Loeb, K. R., ... & Basom, R. S. (2015). Germline ETV6 mutations in familial thrombocytopenia and hematologic malignancy. Nature genetics, 47(2), 180-185.

Noetzli, L., Lo, R. W., Lee-Sherick, A. B., Callaghan, M., Noris, P., Savoia, A., ... & Pecci, A. (2015). Germline mutations in ETV6 are associated with thrombocytopenia, red cell macrocytosis and predisposition to lymphoblastic leukemia. Nature genetics, 47(5), 535-538.

Stockton, S. S., Malhotra, V., Lu, X., Thangavelu, M., Albitar, M., & Cogle, C. R. (2015). Gene Mutations in MDS Associating with Peripheral Blood Count Abnormalities. Blood, 126(23), 1685-1685.

Shen, W., Szankasi, P., Sederberg, M., Schumacher, J., Frizzell, K. A., Gee, E. P., ... & Kelley, T. W. (2016). Concurrent detection of targeted copy number variants and mutations using a myeloid malignancy next generation sequencing panel allows comprehensive genetic analysis using a single testing strategy. British journal of haematology.

Poggi, M., Canault, M., Favier, M., Turro, E., Saultier, P., Ghalloussi, D., ... & Mohand-Oumoussa, B. (2016). Germline variants in ETV6 underlie reduced platelet formation, platelet dysfunction and increased levels of circulating CD34+ progenitors. Haematologica, haematol-2016.

Schwaab, J., Schnittger, S., Sotlar, K., Walz, C., Fabarius, A., Pfirrmann, M., ... & Valent, P. (2013). Comprehensive mutational profiling in advanced systemic mastocytosis. Blood, 122(14), 2460-2466.

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