ALK Mutation (Gene Rearrangement)
- Also Known As:
- EML4-ALK Fusion Protein
- ALK Gene Rearrangement
- ALK Gene Fusion
- Formal Name:
- ALK (Anaplastic Lymphoma Receptor Tyrosine Kinase) Gene Rearrangement
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 health care practitioner is considering a therapeutic management plan that may include an ALK kinase inhibitor such as crizotinib
A tumor tissue sample is obtained through a biopsy procedure or sometimes collected during surgery. The tumor tissue is typically evaluated by a pathologist prior to testing.
Test Preparation Needed?
Usually no preparation is needed.
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 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 regulate cell growth.
About 4-5% 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 (fusion partner). The most common ALK fusion partner is a 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.
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 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 ALK gene rearrangements in tumor tissue.
The test is typically ordered along with or as a follow-up test to EGFR and ROS1. If a non-small cell lung cancer has an EGFR 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.
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 ALK fusions.
- Immunohistochemistry (IHC)—this method detects the altered ALK protein; IHC is an acceptable alternative to FISH.
- Next generation sequencing (NGS) —this method detects ALK fusions and identifies the fusion partner gene, which may have some clinical significance.
- Polymerase chain reaction (PCR)—this method detects known ALK fusions; however, it cannot identify novel fusions.
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.
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.
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.
Should everyone with lung cancer have ALK mutation testing?
Testing is not generally indicated unless a person has non-small cell lung cancer.
Is it necessary to repeat an ALK mutation test?
This is not usually necessary but might occur if the health care practitioner thought that the first sample tested might have been insufficient. In the rare instances where the original biopsy tissue is not sufficient, a new biopsy will be collected from the patient following the biopsy procedure.
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?
Yes, ALK rearrangements could be detected in the DNA of tumor cells that is shed in the blood; however, it is not as reliable as the tissue-based test. Blood testing could be useful when no tissue is available for testing, but the procedure is still investigational.
Sources Used in Current Review
2018 review performed by Mutasim Elfahal, PhD, DABCC.
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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.