ALK Mutation (Gene Rearrangement)
Note: this site is for informational purposes only. To view test results or book a test, use the NHS app in England or contact your GP.
The ALK mutation (gene rearrangement) test is a molecular test on tumour tissue in which a sample of a person’s cancer tissue is analysed in the laboratory to look for specific rearrangements in the ALK gene. It is used to identify non-small cell lung cancers with ALK gene changes that may respond to targeted therapy.
Why get tested?
To detect an ALK gene rearrangement in tumour 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 healthcare professional is considering a therapeutic management plan that may include an ALK kinase inhibitor such as crizotinib, ceritinib and alectinib.
Sample required?
A fresh tumour tissue sample is obtained through a biopsy procedure or sometimes collected during surgery. The tumour 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 tumour tissue.
Common questions
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 tumour tissue.
The test is typically requested along with or as a follow-up test to EGFR. 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 tumour 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 tumour would be likely to respond to an ALK kinase inhibitor.
If a person’s tumour 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.
An ALK mutation test is usually requested after an individual has been diagnosed with non-small cell lung cancer, especially adenocarcinoma.
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 tumour 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.
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.
Testing is not generally indicated unless a person has non-small cell lung cancer.
This is not usually necessary but might occur if the healthcare professional 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.
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.
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.
It may be available in some larger laboratories and hospitals designated as Genomic Laboratory Hubs.
Yes, ALK rearrangements could be detected in the DNA of tumour 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.