ALK Mutation (Gene Rearrangement)

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.