Genetic Testing for Lung Cancer

Why It's Done and How It Can Influence Treatment

Genetic testing is playing a larger role in lung cancer care. These tests can identify specific genetic changes in the tumor cells that might be treatable with targeted therapies.

Among the many benefits of targeted therapies is that they can block growth of cancer cells without harming healthy cells.

Scientist conducting the process of Polymerase chain reaction (PCR) to amplify DNA by using a thermocycler to create samples
Monty Rakusen / Getty Images

The Role of Genetics in Lung Cancer

Lung cancer occurs when cells in the lungs are altered so that they become cancerous. Cancer cells can multiply uncontrollably, and may potentially invade nearby and distant regions. These changes occur due to harmful genetic mutations in the DNA of a lung cell. When a mutated cell multiplies, the newly formed cells carry the same dangerous mutations.

Mutations can occur when a cell exposed to toxins or when the body makes an error during cell division.

All genes are made up of variable sequences of four nucleotide bases—adenine, thymine, cytosine, and guanine. These nucleotides direct your body to make specific proteins. A mutation means that one base is substituted for another, or that bases are inserted, deleted, or rearranged in some way. This will result in an altered protein product.

The two main types of mutations that can lead to cancer are driver mutations and passenger mutations. Driver genes have a direct role in the process by which cancer begins, known as oncogenesis. After initiating the cancer, these mutated genes literally fuel the growth of cancerous cells. In lung cancer, there may be more than one type of driver gene. Researchers have estimated that 51% of lung cancers are positive for known driver mutations.

Passenger mutations, which significantly outnumber the driver mutations, also play a role—although it isn't as significant.

Importance of Genetic Testing

Genetic changes account for about 80% to 85% of non-small cell lung cancer (NSCLC). Mutations are found in about 10% to 15% of small lung cell cancers (SCLC).

If you’ve been recently diagnosed with lung cancer, such as lung adenocarcinoma, a type of NSCLC, you might have genetic testing as a way to identify specific driver mutations that your healthcare providers may be able to target with medications.

Targeted therapies are a form of precision medicine, which means they are selected for you based on precise information about your specific disease. In contrast, conventional chemotherapy is prescribed more broadly for cancer.

The benefits of targeted therapy include:

  • Chemotherapy drugs attack all rapidly dividing cells—cancerous or not—and pose a risk of toxicity. Targeted therapies attack only a particular abnormality present in your cancer cells, which results in less discomfort and a better quality of life during treatment.
  • Some targeted therapies can block angiogenesis, the process by which new blood vessels form—angiogenesis promotes cancer growth.
  • Targeted therapy drugs provide higher response rates and longer progression-free survival rates than chemotherapy.

What Genetic Testing Looks For

As much as is known about genetic abnormalities behind lung cancer, this is a relatively new area of medical science. There is more behind cancer cell growth than what yet been discovered.

Some of the lung cancer mutations that are detectable with genetic testing include:

  • EGFR mutations: This mutation causes the overproduction of epidermal growth factor receptor (EGFR), a protein involved in cell growth and division, which causes the mutated cells to grow too fast. This mutation is common in people with lung cancer who have never smoked.
  • KRAS mutations: When the gene that carries instructions for a KRAS protein is damaged, cells may make an altered protein that can't regulate growth properly.
  • ALK rearrangements:  About 5% of NSCLCs produce abnormal ALK proteins that cause cancer cells to grow and spread. The abnormal proteins are formed due to a fusion of two genes known as anaplastic lymphoma kinase (ALK) and echinoderm microtubule-associated protein-like 4 (EML4).
  • ROS1 rearrangements: About 1 to 2% of NSCLCs have a rearrangement in the ROS1 gene. This mutation is a fusion of ROS1 and another gene and results in the production of an abnormal protein. The ALK and ROS1 rearrangements are so similar that some targeted therapies can work on both conditions.
  • MET amplifications: Some cancers involve a mutation of the mesenchymal-epithelial transition (MET) gene, which causes them to produce abnormal proteins, and leads to cancer growth and spread.
  • BRAF mutations: Common in smokers, this mutation affects B-Raf proteins and can increase cancer spread.
  • RET mutations: An altered RET gene in cancer cells forms RET proteins that cause cell proliferation.
  • NTRK fusions: A fusion between a piece of the chromosome containing an NTRK gene and a gene on another chromosome produces proteins called TRK fusion proteins can lead to abnormal cell growth.

For a sense of the impact of discovering one such mutation, drugs that target EGFR mutations result in a 75% response rate and progression-free survival rates of nine to 13 months. With drugs that target ALK rearrangements, the response rate is 60% with a nine-month progression-free survival rate.

Who Should Be Tested?

Almost all gene mutations related to the disease are acquired. That means they occur because of exposure to carcinogens that damage cell DNA. These are called somatic mutations, and they are not present at birth (and do not run in families). Anyone can develop them, which is why genetic testing for lung cancer is recommended for all patients.

Hereditary lung cancer mutations (also called germline mutations), which are a far less common cause of lung cancer than somatic mutations, are part of your genetic makeup at birth and can be passed down from parent to child, increasing the risk of developing lung cancer.

Driver mutations that result in the development of cancer are estimated to be present in as many as 70% of people with lung adenocarcinoma.

Factors that can increase your risk of developing acquired lung cancer mutations:

  • Tobacco smoke (firsthand and secondhand)
  • Air pollution
  • Radon
  • Asbestos
  • Exposure to certain metals or chemicals
  • Hormone replacement therapy
  • Lung conditions: Tuberculosis, asthma, and COPD are among the diseases that raise the risk of lung cancer. COPD, for instance, raises the risk of lung cancer by two to four times.

Lung Cancer Genetic Testing Methods

If you're diagnosed with any stage of lung cancer, your healthcare provider will likely request tests to check for genetic mutations, which are considered a type of biomarker.

There are two basic types of genomic testing for lung cancer. These involve either taking a tissue sample or a blood sample.

Tissue Biopsy

A tissue biopsy is the standard procedure by which healthcare providers obtain a sample for genetic testing. If your healthcare provider is planning to surgically remove your tumor regardless of its genetic makeup, a sample of the excised tumor will be saved after the operation for analysis.

Many academic cancer centers offer on-site genetic testing, or your oncologist can send your tissue sample out to companies and laboratories for comprehensive testing.

Blood Testing

A liquid biopsy is a blood test that can be used to check for cancer cells circulating in the blood and can be used to detect genetic mutations in these cells. It may be used in addition to a tissue biopsy.

Advantages of liquid biopsy:

  • Does not pose a risk of infection, pneumothorax (collapsed lung), or other complications associated with tissue biopsy
  • Offers a good alternative if the tumor is in a hard-to-access place
  • Lets healthcare providers easily compare multiple samples over time to see how you are responding to treatment

How Results Advise Treatment


Whether or not you receive a targeted therapy alone or in conjunction with other treatment depends on your case and type of lung cancer. Based on the mutations identified, you may be matched with a targeted drug or qualified to enter a clinical trial.

Your healthcare provider will consider the drug options approved for your specific mutation (if any). For example, while ALK rearrangements may be treated with one of five different drugs approved by the U.S. Food and Drug Administration (FDA), only one drug is approved for MET amplification.

Identifying mutations can also give your healthcare provider additional information, such as how likely it may be for cancer to recur. This may help with other treatment decisions, such as surgery.

There are several therapies available to target specific mutations that may be involved in lung cancer, and research is ongoing to develop more.

Resistance to Treatment

Discovering a treatable mutation via genetic testing for lung cancer can help your healthcare providerrs form a tailored treatment plan for you. However, nearly everyone inevitably becomes resistant to currently available targeted treatments with time.

A Word From Verywell

The ability to understand the molecular profile of lung tumors is an exciting area of research, and it’s likely that targeted therapies for newly identified mutations will continually be made available as clinical trials pursue more effective options.

If you have been diagnosed with lung cancer, especially lung adenocarcinoma or squamous cell lung cancer, talk to your healthcare provider about genetic testing. If your results show a genetic biomarker, research the treatments available and connect with others who have the same diagnosis. There are many hopeful opportunities for those with these types of cancer.

Was this page helpful?
12 Sources
Verywell Health uses only high-quality sources, including peer-reviewed studies, to support the facts within our articles. Read our editorial process to learn more about how we fact-check and keep our content accurate, reliable, and trustworthy.
  1. Sequist LV, Heist RS, Shaw AT, et al. Implementing multiplexed genotyping of non-small-cell lung cancers into routine clinical practice. Ann Oncol. 2011;22(12):2616-2624. doi:10.1093%2Fannonc%2Fmdr489

  2. Brown AL, Li M, Goncearenco A, Panchenko AR. Finding driver mutations in cancer: Elucidating the role of background mutational processes. PLoS Comput Biol. 2019;15(4):e1006981. doi:10.1371/journal.pcbi.1006981

  3. American Cancer Society. What is lung cancer? Updated October 1, 2019.

  4. American Cancer Society. Targeted drug therapy for non-small cell lung cancer. Updated October 1, 2019.

  5. Ye M, Zhang X, Li N, et al. ALK and ROS1 as targeted therapy paradigms and clinical implications to overcome crizotinib resistanceOncotarget. 2016;7(11):12289-12304.

  6. Kanwal M, Ding XJ, Cao Y. Familial risk for lung cancer. Oncol Lett. 2017;13(2):535-542. doi:10.3892%2Fol.2016.5518

  7. Grosse A, Grosse C, Rechsteiner M, Soltermann A. Analysis of the frequency of oncogenic driver mutations and correlation with clinicopathological characteristics in patients with lung adenocarcinoma from Northeastern SwitzerlandDiagn Pathol. 2019;14(1):18. doi:10.1186/s13000-019-0789-1

  8. MedlinePlus. Lung cancer. Updated August 18, 2020.

  9. Durham AL, Adcock IM. The relationship between COPD and lung cancerLung Cancer. 2015;90(2):121-7. doi:10.1016/j.lungcan.2015.08.017

  10. National Cancer Institute. Tumor DNA sequencing in cancer treatment. Updated October 5, 2017.

  11. Lung Cancer Foundation of America. What do I need to know about genetic mutation testing?

  12. Liam CK. Central nervous system activity of first-line osimertinib in epidermal growth factor receptor-mutant advanced non-small cell lung cancerAnn Transl Med. 2019;7(3):61. doi:10.21037/atm.2018.12.68

Additional Reading