What are other Names for this Test? (Equivalent Terms)
- ATRX Gene Mutation Test
- ATRX Gene Sequencing Test
- ATRX Mutation Test
What is ATRX Mutation Analysis Test? (Background Information)
- ATRX mutation is an alteration in the ATRX gene, which gives instructions for the ATRX protein (which is also called X-linked helicase II, X-linked nuclear protein, or XNP)
- ATRX mutations are associated with the following conditions:
- Grades II and III astrocytomas (71% of the cases)
- Glioblastoma (71% of the cases)
- Oligoastrocytomas (68% of the cases)
- Pancreatic neuroendocrine tumors (19% of the cases)
- Myelodysplastic syndrome (or MDS, in 13% of the cases)
- Endometrial tumors (10% of the cases)
- Colon cancer (8% of the cases)
- Lung cancers (7% of the cases)
- The ATRX protein plays a role in regulating protein production. Proteins are normally produced by specialized cellular machinery using instructions provided by the genetic blueprint
- Access to a given region of the genetic blueprint, and thus, the extent of production of the protein associated with that region of DNA, is tightly controlled
- The ATRX protein helps control the availability of certain regions of DNA to the protein production machinery, and hence, the degree to which those regions of DNA yield protein products
- Mutations in the ATRX gene may cause defects in the ATRX protein. The ATRX protein is involved in regulating production of proteins involved in cellular growth and division. Thus, defects in the ATRX protein may lead to uncontrolled cell growth and division, and hence, to cancer
- The ATRX Mutation Analysis Test detects abnormalities in the ATRX gene. It is used to guide therapy for cancer 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 ATRX Mutation Analysis Test?
Following are the clinical indicators for performing the ATRX Gene Mutation Analysis Test:
- Monitoring cancer therapy
- Assessing treatment options for brain, lung, colon, and other cancers
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 ATRX Mutation Analysis Test?
Following is the specimen collection process for ATRX 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 ATRX 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 ATRX Mutation Analysis Test Result?
• A positive value for the ATRX Mutation Analysis Test may disqualify certain therapeutic drugs from being used to treat brain, lung, colon, and other cancers
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:
- Mutations in the ATRX gene often occur alongside mutations in the IDH1 and IDH2 genes
- 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?
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)
NeoGenomics Laboratories. (2016). ATRX mutation analysis.
https://www.genetests.org/genes/?gene=ATRX (accessed on 05/10/2017)
http://www.imm.ox.ac.uk/protocol-for-atr-x-testing (accessed on 05/10/2017)
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
Sausen, M., Leary, R. J., Jones, S., Wu, J., Reynolds, C. P., Liu, X., ... & Vogelstein, B. (2013). Integrated genomic analyses identify ARID1A and ARID1B alterations in the childhood cancer neuroblastoma. Nature genetics, 45(1), 12-17.
Kannan, K., Inagaki, A., Silber, J., Gorovets, D., Zhang, J., Kastenhuber, E. R., ... & Huse, J. T. (2012). Whole-exome sequencing identifies ATRX mutation as a key molecular determinant in lower-grade glioma. Oncotarget, 3(10), 1194-1203.
Jiao, Y., Killela, P. J., Reitman, Z. J., Rasheed, B. A., Heaphy, C. M., de Wilde, R. F., ... & Bettegowda, C. (2012). Frequent ATRX, CIC, FUBP1 and IDH1 mutations refine the classification of malignant gliomas. Oncotarget, 3(7), 709-722.
Khuong-Quang, D. A., Buczkowicz, P., Rakopoulos, P., Liu, X. Y., Fontebasso, A. M., Bouffet, E., ... & Bourgey, M. (2012). K27M mutation in histone H3. 3 defines clinically and biologically distinct subgroups of pediatric diffuse intrinsic pontine gliomas. Acta neuropathologica, 124(3), 439-447.
Wilson, R. K., & Mardis, E. R. (2015). Genomic landscape of paediatric adrenocortical tumours.
Steensma, D. P., Bejar, R., Jaiswal, S., Lindsley, R. C., Sekeres, M. A., Hasserjian, R. P., & Ebert, B. L. (2015). Clonal hematopoiesis of indeterminate potential and its distinction from myelodysplastic syndromes. Blood, 126(1), 9-16.
Cai, J., Yang, P., Zhang, C., Zhang, W., Liu, Y., Bao, Z., ... & Jiang, C. (2014). ATRX mRNA expression combined with IDH1/2 mutational status and Ki-67 expression refines the molecular classification of astrocytic tumors: evidence from the whole transcriptome sequencing of 169 samples samples. Oncotarget, 5(9), 2551-2561.
Ikemura, M., Shibahara, J., Mukasa, A., Takayanagi, S., Aihara, K., Saito, N., ... & Fukayama, M. (2016). Utility of ATRX immunohistochemistry in diagnosis of adult diffuse gliomas. Histopathology.