Also Known As
EML4-ALK Fusion Protein
ALK Gene Rearrangement
ALK Gene Fusion
Formal Name
ALK (Anaplastic Lymphoma Receptor Tyrosine Kinase) Gene Rearrangement
This article was last reviewed on
This article waslast modified on
January 15, 2018.
At a Glance
Why Get Tested?

To detect an ALK gene rearrangement in tumor tissue in order to guide non-small cell lung cancer therapy

When To Get Tested?

When you have been diagnosed with non-small cell lung cancer and your doctor is considering a therapeutic management plan that may include an ALK kinase inhibitor such as crizotinib

Sample Required?

A sample of tumor tissue

Test Preparation Needed?

None

You may be able to find your test results on your laboratory's website or patient portal. However, you are currently at Lab Tests Online. You may have been directed here by your lab's website in order to provide you with background information about the test(s) you had performed. You will need to return to your lab's website or portal, or contact your healthcare practitioner in order to obtain your test results.

Lab Tests Online is an award-winning patient education website offering information on laboratory tests. The content on the site, which has been reviewed by laboratory scientists and other medical professionals, provides general explanations of what results might mean for each test listed on the site, such as what a high or low value might suggest to your healthcare practitioner about your health or medical condition.

The reference ranges for your tests can be found on your laboratory report. They are typically found to the right of your results.

If you do not have your lab report, consult your healthcare provider or the laboratory that performed the test(s) to obtain the reference range.

Laboratory test results are not meaningful by themselves. Their meaning comes from comparison to reference ranges. Reference ranges are the values expected for a healthy person. They are sometimes called "normal" values. By comparing your test results with reference values, you and your healthcare provider can see if any of your test results fall outside the range of expected values. Values that are outside expected ranges can provide clues to help identify possible conditions or diseases.

While accuracy of laboratory testing has significantly evolved over the past few decades, some lab-to-lab variability can occur due to differences in testing equipment, chemical reagents, and techniques. This is a reason why so few reference ranges are provided on this site. It is important to know that you must use the range supplied by the laboratory that performed your test to evaluate whether your results are "within normal limits."

For more information, please read the article Reference Ranges and What They Mean.

What is being tested?

ALK is a short name for the anaplastic lymphoma receptor tyrosine kinase gene. This test detects specific rearrangements in the ALK gene in the DNA of cancer cells and tissue. The presence of these changes makes it more likely that a person with non-small cell lung cancer will respond to a targeted drug therapy.

The ALK gene codes for a protein called anaplastic lymphoma kinase. It is part of a family of proteins called receptor tyrosine kinases that transmit signals into cells and are thought to help regulate the proliferation of nerve cells.

About 5% of people who have non-small cell lung cancer, the most common type of lung cancer, have an alteration on chromosome 2 that leads to the fusion of the ALK gene with another gene called EML4 and results in the production of an EML4-ALK fusion protein. It is a rare mutation most commonly seen in people who have never smoked or are light smokers, especially women of Asian descent.

This gene mutation and abnormal protein production promotes the uncontrolled growth of cancer cells, but it also makes it more likely that the affected person will respond to a drug that targets the abnormal protein (an ALK kinase inhibitor, such as crizotinib) and less likely that the person will respond to tyrosine kinase inhibitors that target the EGFR (epidermal growth factor receptor).

There are several different methods of testing for ALK mutations, but all of them involve evaluating either the ALK gene rearrangement or the altered ALK protein in tumor tissue.

How is the sample collected for testing?

A tumor tissue sample is obtained through a biopsy procedure or sometimes collected during a surgery. The tumor tissue is typically evaluated by a pathologist prior to testing.

Is any test preparation needed to ensure the quality of the sample?

No test preparation is needed.

Accordion Title
Common Questions
  • How is it used?

    ALK mutation analysis is used primarily to determine if a person with adenocarcinoma non-small cell lung cancer is likely to respond to an ALK kinase inhibitor drug therapy, such as crizotinib. This testing detects the presence of the most common ALK gene rearrangements in the DNA of cells in tumor tissue or the abnormal protein produced by the mutated gene in order to help guide cancer treatment.

    This testing is typically ordered along with or as a follow-up test to EGFR and KRAS mutation testing. If a non-small cell lung cancer has an EGFR mutation and lacks a KRAS mutation, then the affected person is likely to respond to an anti-EGFR drug therapy (tyrosine kinase inhibitor) and further testing is usually not necessary. However, if the tumor is negative for an EGFR mutation, then the person is not likely to respond to an anti-EGFR tyrosine kinase inhibitor. ALK mutation testing is then used to determine whether the person's tumor would be likely to respond to an ALK kinase inhibitor.

    If a person's tumor is negative for the most common ALK gene rearrangements, tests for other less common mutations not detected by the current test or tests for the altered ALK protein may be used to help predict therapeutic responses. In some cases, testing for the altered ALK protein may be preferred over ALK gene rearrangement testing.

    Two main methods of testing include:

    • Fluorescent in situ hybridization (FISH)—this method looks at the genetic level for presence of the gene rearrangement; it is currently the gold standard for evaluating non-small cell lung cancer tumors.
    • Immunohistochemistry (IHC)—this method detects the altered ALK protein; IHC is not widely available but is gaining in use.
  • When is it ordered?

    An ALK mutation test is usually ordered after an individual has been diagnosed with non-small cell lung cancer, especially adenocarcinoma. It is ordered when a person's tumor is unlikely to respond to a tyrosine kinase inhibitor and the health practitioner is considering an ALK kinase inhibitor drug therapy.

  • What does the test result mean?

    If the cancer tissue contains a specific ALK gene rearrangement mutation or altered ALK protein, then the affected person is likely to benefit from an ALK kinase inhibitor drug therapy such as crizotinib and is not likely to benefit from anti-EGFR drug therapies.

    A person whose cancer does not have an ALK gene rearrangement is not likely to benefit from ALK kinase inhibitor drug therapy.

    A person could have a negative test result if the tumor tissue sample is insufficient and/or when the cancer is heterogeneous (some cells contain the mutation and others do not). Additionally, there may be rare ALK mutations that are not detected by routine testing that looks for only the most common mutations.

  • Is there anything else I should know?

    ALK gene rearrangements are most often seen in light smokers or non-smokers with adenocarcinoma non-small cell lung cancers, especially women of Asian descent. Although this is a relatively rare mutation, the total number of people affected by lung cancer each year means that the test and potential drug therapy is applicable to thousands of people.

    ALK mutations may also be seen in some T-cell lymphomas.

  • Should everyone with lung cancer have ALK mutation testing?

    Testing is not generally indicated unless a person has non-small cell lung cancer and a health practitioner is considering ALK kinase inhibitor drug therapy.

  • Is it necessary to repeat an ALK mutation test?

    This is not usually necessary but might occur if the health practitioner thought that the first sample tested might have been insufficient.

  • Can I receive ALK kinase inhibitor drug therapy and still not benefit from it?

    Yes, most people whose lung cancer has the ALK gene rearrangement will respond, but a percentage will not. Each person and each cancer is different. Also, a person may respond initially and then become resistant to the treatment.

  • Can I take an ALK kinase inhibitor drug therapy without being tested?

    In most cases, this is not recommended. The drugs have been developed with specific associations and your lung cancer is not likely to respond if you do not meet the identified criteria.

  • Can this test be performed by my local laboratory?

    It may be available in some larger laboratories and hospitals designated as Comprehensive Cancer Centers by the National Cancer Institute, but most often it will be sent to a reference laboratory.

  • Can this test be performed on my blood instead?

    No, it is not the genetics of the person that is being evaluated; it is the genetic makeup of the cancer.

View Sources

Markman, M. (Updated 2013 July 15). Genetics of Non-Small Cell Lung Cancer. Medscape Reference [On-line information]. Available online at http://emedicine.medscape.com/article/1689988-overview through http://emedicine.medscape.com. Accessed July 2013.

Lindeman, N. et. al. (2013 June). Molecular Testing Guideline for Selection of Lung Cancer Patients for EGFR and ALK Tyrosine Kinase Inhibitors, Guideline from the College of American Pathologists, International Association for the Study of Lung Cancer, and Association for Molecular Pathology. Arch Pathol Lab Med v 137, [On-line information]. Available online at http://www.archivesofpathology.org/doi/pdf/10.5858/arpa.2012-0720-OA through http://www.archivesofpathology.org. Accessed July 2013.

Wallander, M. et. al. (Updated 2013 July) Lung Cancer. ARUP Consult [On-line information]. Available online at http://www.arupconsult.com/Topics/LungCancer.html?client_ID=LTD through http://www.arupconsult.com. Accessed July 2013.

(Revised 2012 March 21). Crizotinib. American Cancer Society [On-line information]. Available online at http://www.cancer.org/treatment/treatmentsandsideeffects/guidetocancerdrugs/crizotinib through http://www.cancer.org. Accessed July 2013.

Chustecka, Z. (2012 September 30). Crizotinib Now Standard of Care for ALK+ NSCLC. Medscape Medical News from the 2012 European Society for Medical Oncology (ESMO) Congress [On-line information]. Available online at http://www.medscape.com/viewarticle/771853 through http://www.medscape.com. Accessed July 2013.

Markman, M. (2012 April 4). How Does Genetics Affect Outcomes in Nonsmokers With NSCLC? Medscape Today News from Cancer v 118: 729-739. [On-line information]. Available online at http://www.medscape.com/viewarticle/761054 through http://www.medscape.com. Accessed July 2013.

(2013 June 17). Crizotinib Improves Progression-Free Survival in Some Patients with Advanced Lung Cancer. National Cancer Institute [On-line information]. Available online at http://www.cancer.gov/clinicaltrials/results/summary/2013/crizotinib-NSCLC0613 through http://www.cancer.gov. Accessed July 2013.

(Reviewed 2011 March). ALK. Genetics Home Reference [On-line information]. Available online at http://ghr.nlm.nih.gov/gene/ALK through http://ghr.nlm.nih.gov. Accessed July 2013.

Mulcahy, N. (2012 March 22). NSCLC Guidelines From NCCN Full of Change. Medscape Medical News [On-line information]. Available online at http://www.medscape.com/viewarticle/760722 through http://www.medscape.com. Accessed July 2013.

(Updated 2010 June) Getting the Facts, Anaplastic Large Cell Lymphoma. Lymphoma Research Foundation [On-line information]. Available online at http://www.lymphoma.org/atf/cf/%7B0363cdd6-51b5-427b-be48-e6af871acec9%7D/ANAPLASTIC10.PDF through http://www.lymphoma.org. Accessed July 2013.

(2012 May 16). Drug used in NIH-supported trial shows benefit in children with previously treated cancers. National Cancer Institute [On-line information]. Available online at http://www.cancer.gov/newscenter/newsfromnci/2012/crizotinib through http://www.cancer.gov. Accessed July 2013.

Nelson, R. (2011 August 26). FDA Approves New Drug for Advanced NSCLC. Medscape Medical News [On-line information]. Available online at http://www.medscape.com/viewarticle/748675 through http://www.medscape.com. Accessed July 2013.

Nelson, R. (2012 October 25). Crizotinib Receives Conditional Marketing Approval in Europe. Medscape Medical News [On-line information]. Available online at http://www.medscape.com/viewarticle/773280 through http://www.medscape.com. Accessed July 2013.

(Revised 2012 October 18). Tumor Markers. American Cancer Society [On-line information]. Available online through http://www.cancer.org. Accessed July 2013.

Yi E., et al. Correlation of IHC and FISH for ALK Gene Rearrangement in Non-small Cell Lung Carcinoma: IHC Score Algorithm for FISH. Journal of Thoracic Oncology March 2011 - Volume 6 - Issue 3 - Pp 459-465. Available online at http://journals.lww.com/jto/Fulltext/2011/03000/Correlation_of_IHC_and_FISH_for_ALK_Gene.8.aspx# through http://journals.lww.com. Accessed November 2013.

Gregory J. Tsongalis, PhD, HCLD, CC, Professor of Pathology, Director, Molecular Pathology, Dartmouth Hitchcock Medical Center and Geisel School of Medicine at Dartmouth, Lebanon, NH.

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