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CBL Mutation Analysis Test

Last updated Feb. 1, 2017

The CBL Mutation Analysis Test detects abnormalities in the CBL gene. It is used to diagnose lymphomas such as JMML. It also helps guide treatment for lymphomas by aiding in the selection of therapeutic drugs, and disqualifying certain drugs from being used.

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

  • CBL2 Mutation Analysis Test
  • FRA11B Mutation Analysis Test
  • RNF55 Mutation Analysis Test

What is CBL Mutation Analysis Test? (Background Information)

  • CBL mutation refers to an alteration in the CBL gene, which is associated with cancers of the lymphatic system (lymphomas). Among these is juvenile myelomonocytic leukemia (JMML), an aggressive form of clonal myeloproliferative disorder (MPD) affecting children
  • CBL gives instructions for the CBL protein. The CBL protein is an enzyme responsible for marking proteins for degradation by the cells’ recycling machinery, a process called ubiquitination
  • Proteins “tagged” by CBL are recognized by the proteasome, a complex of proteins that acts as a garbage disposal in the cell. Proteins ubiquitinated by CBL are soon destroyed by the proteasome; thus, ubiquitination by CBL is referred to as a “molecular kiss of death”
  • Through its ability to mark proteins for destruction, CBL plays a crucial role in controlling important signaling and growth pathways in the cell. For example, by restraining the numbers of a class of proteins called receptor tyrosine kinases (RTKs), CBL can indirectly control the growth and division of a cell
  • Any anomalies in the CBL gene may lead to the production of a defective CBL protein. This may cause widespread harm in cells, such as by preventing the ability to degrade RTKs and thus restrict cell growth. This may result in the development of cancer
  • The CBL Mutation Analysis Test detects abnormalities in the CBL gene. It is used to diagnose lymphomas such as JMML. It also helps guide treatment for lymphomas by aiding in the selection of therapeutic drugs, and disqualifying certain drugs from being used

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 CBL Mutation Analysis Test?

Following are the clinical indicators for performing the CBL Mutation Analysis Test: 

  • Swollen, but painless, lymph nodes
  • Abdominal swelling
  • Fatigue
  • Easy bruising
  • Bone and joint pain
  • Recurrent infections
  • Fever, night sweats

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 CDL Mutation Analysis Test?

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

A mutation in the CDL gene means a positive result for the CDL Mutation Analysis Test. This may point to the following diagnoses:

  • Juvenile myelomonocytic leukemia (JMML)
  • Noonan syndrome-like disorder with or without JMML

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:

  • CBL mutation most notably occurs in a location of the chromosome called 11q23.3 - i.e., the long arm (q) of chromosome 11 in position 23.3
  • 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)

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

Juvenile Myelomonocytic Leukemia (JMML). (n.d.). Retrieved from http://kidshealth.org/en/parents/jmml.html

Mutations in CBL occur frequently in juvenile myelomonocytic leukemia | Blood Journal. (n.d.). Retrieved from http://www.bloodjournal.org/content/114/9/1859?sso-checked=true

OMIM Entry - * 165360 - CAS-BR-M MURINE ECOTROPIC RETROVIRAL TRANSFORMING SEQUENCE HOMOLOG; CBL. (n.d.). Retrieved from http://www.omim.org/entry/165360

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