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CALR Mutation Analysis Test

Last updated May 26, 2017

Approved by: Maulik P. Purohit MD MPH

The CALR Mutation Analysis Test detects abnormalities in the CALR gene. It helps diagnose myeloproliferative neoplasm.


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

  • Calreticulin Mutation Analysis Test

What is CALR Mutation Analysis Test? (Background Information)

  • CALR mutation refers to an alteration in the CALR gene, which is associated with a class of bone marrow cancers called myeloproliferative neoplasms (MPNs)
  • CALR gives instructions for calreticulin, a protein that protects cells from damaged proteins and other molecules. Through its protection of cells, calreticulin helps prevent cancer and other disorders
  • Calreticulin protects cells, by helping rid them of misfolded or defective proteins. Calreticulin marks misfolded proteins for destruction by the cellular degradation machinery
  • Cells that possess a CALR mutation produce a faulty calreticulin protein that is unable to protect them from misfolded proteins
  • CALR mutation that occurs in developing blood cells, called hematopoietic stem cells, may result in a class of blood cell cancers called myeloproliferative neoplasms
  • MPN are characterized by overproduction of red blood cells, white blood cells, or platelets. This is a result of hematopoietic stem cells’ inability to properly regulate the production of these blood cells (essential thrombocytosis, or ET)
  • CALR mutation may also cause scarring of bone marrow tissue. This is called primary myelofibrosis
  • The CALR Mutation Analysis Test detects abnormalities in the CALR gene. It helps diagnose myeloproliferative neoplasm. It may also aid in monitoring therapy for MPN and detecting recurrence of MPN

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 CALR Mutation Analysis Test?

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

  • Weakness, fatigue
  • Abdominal pain
  • Fullness
  • Bruising easily and persistent bleeding
  • Bluish fingers and toes
  • Headaches
  • Disturbed vision
  • Dizziness

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 CALR Mutation Analysis Test?

Following is the specimen collection process for CALR 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 CALR 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 CALR Mutation Analysis Test Result?

  • A mutation in the CALR gene means a positive result for the CALR Mutation Analysis Test. This may point to a diagnosis of myeloproliferative neoplasm (MPN)

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:

  • CALR mutations are present in 50-71% of essential thrombocythemia, and 56-88% of primary myelofibrosis that are negative for JAK2 and MPL mutations
  • 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, 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/primary-myelofibrosis/

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)

Bloodwise. (2016). Symptoms and diagnosis: myeloproliferative neoplasms (MPN).

Mutation of the calreticulin (CALR) gene in myeloproliferative neoplasms. (2015, January 8). The Hematologist, 12(1).

Quest Diagnostics. (2016). Calreticulin (CALR), Mutation Analysis. Retrieved from http://www.questdiagnostics.com/testcenter/TestDetail.action?ntc=92074

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

Rumi, E., Pietra, D., Ferretti, V., Klampfl, T., Harutyunyan, A. S., Milosevic, J. D., ... & Milanesi, C. (2014). JAK2 or CALR mutation status defines subtypes of essential thrombocythemia with substantially different clinical course and outcomes. Blood, 123(10), 1544-1551.

Nangalia, J., Massie, C. E., Baxter, E. J., Nice, F. L., Gundem, G., Wedge, D. C., ... & Aziz, A. (2013). Somatic CALR mutations in myeloproliferative neoplasms with nonmutated JAK2. New England Journal of Medicine, 369(25), 2391-2405.

Tefferi, A., Lasho, T. L., Finke, C. M., Knudson, R. A., Ketterling, R., Hanson, C. H., ... & Pardanani, A. (2014). CALR vs JAK2 vs MPL-mutated or triple-negative myelofibrosis: clinical, cytogenetic and molecular comparisons. Leukemia, 28(7), 1472-1477.

Rumi, E., Pietra, D., Pascutto, C., Guglielmelli, P., Martínez-Trillos, A., Casetti, I., ... & Sant’Antonio, E. (2014). Clinical effect of driver mutations of JAK2, CALR, or MPL in primary myelofibrosis. Blood, 124(7), 1062-1069.

Tefferi, A., Lasho, T. L., Finke, C., Belachew, A. A., Wassie, E. A., Ketterling, R. P., ... & Pardanani, A. (2014). Type 1 vs type 2 calreticulin mutations in primary myelofibrosis: differences in phenotype and prognostic impact. Leukemia, 28(7), 1568.

Tefferi, A., Lasho, T. L., Finke, C., Belachew, A. A., Wassie, E. A., Ketterling, R. P., ... & Pardanani, A. (2014). Type 1 vs type 2 calreticulin mutations in primary myelofibrosis: differences in phenotype and prognostic impact. Leukemia, 28(7), 1568.

Reviewed and Approved by a member of the DoveMed Editorial Board
First uploaded: May 26, 2017
Last updated: May 26, 2017