What are other Names for this Test? (Equivalent Terms)
- Caspase Recruitment Domain Family Member 11 Mutation Analysis Test
What is CARD11 Mutation Analysis Test? (Background Information)
- CARD11 mutation refers to an alteration in the CARD11 gene, which is associated with cancer of the lymphocytes (lymphoma). The mutation is linked to diffuse large B cell lymphoma (DLBCL); the most common form of non-Hodgkin’s lymphoma
- The CARD11 gene gives instructions for a protein necessary for the NF-kB pathway. NF-kB is a signaling framework used by immune cells, such as lymphocytes, to survive, grow, divide, and differentiate
- NF-kB is also a protective mechanism that guards against lymphocytes turning into cancer cells. CARD11 plays a structural role in the process, enabling the many proteins of the NF-kB pathway to properly perform their functions
- Unfortunately, mutations in the CARD11 gene result in a defective CARD11 protein that causes the NF-kB pathway to work incorrectly in lymphocytes. The result is an increased risk for cancers such as DLBCL
- The CARD11 Mutation Analysis Test is a genetic test to detect abnormalities in the CARD11 gene. It aids in diagnosis of diffuse large B cell lymphoma. It also aids in the treatment of DLBCL by guiding selection of therapeutic drugs, including 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 CARD11 Mutation Analysis Test?
Following are the clinical indications for performing the CARD11 Mutation Analysis Test:
- Swollen, but painless, lymph nodes
- Abdominal swelling
- Fever, night sweats
- Rapid, unexplained weight loss
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 CARD11 Mutation Analysis Test?
Following is the specimen collection process for CARD11 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 CARD11 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 CARD11 Mutation Analysis Blood Test Result?
- A mutation in the CARD11 gene means a positive result for the CARD11 Mutation Analysis Blood Test
- This may point to a diagnosis of diffuse large B-cell lymphoma (DLBCL)
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:
- 9.6% cases of DLBCL cases involving the least curable variant (ABC subtype) involve a mutation in the CARD11 gene
- 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)
Diffuse large B-cell lymphoma | Lymphoma Association. (n.d.). Retrieved from https://www.lymphomas.org.uk/about-lymphoma/types/non-hodgkin-lymphoma/diffuse-large-b-cell-lymphoma
GeneCards. (2016). CARD11 Gene (Protein Coding).
Lamason, R. L., McCully, R. R., Lew, S. M., & Pomerantz, J. L. (2010). Oncogenic CARD11 Mutations Induce Hyperactive Signaling by Disrupting Autoinhibition by the PKC-Responsive Inhibitory Domain. Biochemistry, 49(38), 8240-8250. doi:10.1021/bi101052d
Lenz, G., Davis, R. E., & Ngo, V. N. (2008). Oncogenic CARD11 mutations in human diffuse large B cell lymphoma. Science, 319(5870), 1676-9.
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
Hunter, Z. R., Xu, L., Yang, G., Zhou, Y., Liu, X., Cao, Y., ... & Treon, S. P. (2014). The genomic landscape of Waldenström macroglobulinemia is characterized by highly recurring MYD88 and WHIM-like CXCR4 mutations, and small somatic deletions associated with B-cell lymphomagenesis. Blood, 123(11), 1637-1646.
Bouska, A., Zhang, W., Gong, Q., Iqbal, J., Scuto, A., Vose, J., ... & Gascoyne, R. D. (2016). Combined copy number and mutation analysis identifies oncogenic pathways associated with transformation of follicular lymphoma. Leukemia.
Arcaini, L., Rossi, D., Lucioni, M., Nicola, M., Bruscaggin, A., Fiaccadori, V., ... & Casaluci, G. M. (2014). The NOTCH pathway is recurrently mutated in diffuse large B cell lymphoma associated with hepatitis C virus infection. Haematologica, haematol-2014.
Fuchs, S., Rensing-Ehl, A., Pannicke, U., Lorenz, M. R., Fisch, P., Jeelall, Y., ... & Schmitt-Graeff, A. (2015). Omenn syndrome associated with a functional reversion due to a somatic second-site mutation in CARD11 deficiency. Blood, 126(14), 1658-1669.
Wu, C., de Miranda, N. F., Chen, L., Wasik, A. M., Mansouri, L., Jurczak, W., ... & Peng, R. (2016). Genetic heterogeneity in primary and relapsed mantle cell lymphomas: Impact of recurrent CARD11 mutations. Oncotarget, 7(25), 38180-38190.
Greil, J., Rausch, T., Giese, T., Bandapalli, O. R., Daniel, V., Bekeredjian-Ding, I., ... & Korbel, J. O. (2013). Whole-exome sequencing links caspase recruitment domain 11 (CARD11) inactivation to severe combined immunodeficiency. Journal of Allergy and Clinical Immunology, 131(5), 1376-1383.