Lung Cancer

Biomarker Testing for Genetic Mutations in Non-Small Cell Lung Cancer

The DNA in our cells plays a crucial role in determining how each cell grows, changes, and functions. However, if the DNA mutates over time, it can negatively affect the proper growth and division of cells. This ultimately leads to abnormal cell behavior that could develop into cancer.

Genetic mutations are either somatic or germline mutations. Germline mutations are inherited from one (or both) parents. Somatic mutations are not inherited from a parent. They are caused by external factors such as exposure to harmful chemicals or toxins. Somatic genetic mutations are associated with the development of lung cancer, with the primary exposure being chemicals in cigarette smoke.

Several gene mutations are associated with the development of non-small lung cancer (NSCLC). Some patients have no detectable genetic mutations, some have one mutation, and others have several. Based on the results of biomarker tests, the oncologist can create a treatment plan personalized to the specific genetic mutations found during testing. The absence of genetic mutations also provides important information to the oncology team when developing a treatment plan.

Genes Tested for Mutations Leading to Non-Small Cell Lung Cancer

A mutated gene can cause lung cells to grow uncontrollably and/or cause an overgrowth of proteins that fuel the growth of the cancer cells. More than one gene may have changed over time. Currently, your oncologist can test for several gene mutations associated with non-small cell lung cancer. This is called biomarker testing. It’s also sometimes referred to as genomic testing or molecular testing. The following genes are evaluated during the biomarker test:


Epidermal growth factor receptor, or EGFR, accounts for approximately 23% of NSCLC diagnosis. This gene determines how cells grow and divide, and any mutations can lead to uncontrollable cell replication. Patients whose lung cancer is related to an EGFR mutation are typically diagnosed with an EGFR-positive cancer.


The MET gene mutation is a common finding in non-small cell lung cancer genetic test results. However, there are two distinct ways in which this mutation can lead to cancer.

The first way is through MET gene amplification, which means additional copies of the MET gene exist. As MET is a growth receptor, the extra copies cause cancer cells to grow more quickly.

The second way the MET gene mutation can result in cancer is through Exon 14 skipping. This occurs when a crucial step is skipped in the cell breakdown process. Generally, when the MET protein is no longer required, another protein called CBL works with the Exon 14 gene to break it down. However, when CBL joins with the other gene mutation related to MET, it leads to Exon 14 skipping. When the MET gene is mutated, the Exon 14 gene is skipped, causing the MET protein to stay longer than it should, which ultimately promotes cancer growth.


The TP53 gene produces a protein called P53, which helps to suppress damaged cells and prevent additional cell replication. Stopping cell replication is a process that is typically associated with reducing the risk of developing cancer. Mutations in TP53 are present in approximately 50% of NSCLC cases, but testing for this gene is not typically recommended because there are currently no targeted therapies available to counteract the mutation. However, clinical research is underway to determine if the mutation can be countered to slow the growth of lung cancer cells.


The KRAS gene produces the K-RAS protein, which relays signals that control cell replication and differentiation. Mutations in KRAS are found in about 30% of NSCLC cases and are particularly common in patients with a history of smoking. The mutation can also occur in combination with other genetic mutations.


The FGFR1 mutation affects cell growth and spread and is found in up to 20% of non-small cell lung cancer patients. It is more likely to occur in patients with a history of smoking and those with the squamous carcinoma type of NSCLC.


The anaplastic lymphoma kinase, or ALK gene, is commonly linked with lymphoma but can also be found in non-small cell lung cancer. This gene is responsible for creating a developing fetus's gut and nervous system. Typically, it is turned off before birth, but sometimes it can reactivate or fuse with other genes, which can lead to cancer.

The mutations caused by this gene, known as ALK rearrangement or ALK fusion, affect up to 7% of NSCLC patients. Younger lung cancer patients and non-smokers are more likely to have these mutations.


The ROS1 gene fusion is a genetic mutation rarely seen in non-small cell lung cancer patients. It occurs in about 1-2% of individuals with NSCLC. This mutation is caused by the ROS1 gene fusing with another gene, leading to uncontrolled cell growth and, ultimately, cancer. ROS1 is found more often in younger patients and those without a history of smoking.


The BRAF protein helps regulate the rate of cell growth. Mutations in this gene produce an abnormal protein, which signals cells to grow and leads to increased cell growth and cancer. The BRAF protein usually works with the MEK protein to regulate cell growth. In patients with the BRAF mutation, lung cancer specialists may discuss the MEK protein. This mutation is responsible for about 3-4% of NSCLC diagnoses and is more common in patients with a history of smoking.


NTRK gene fusions are present in many different types of cancer, including non-small cell lung cancer, although rare (less than 1% of cases). No one type of patient is most likely to have an NTRK gene fusion.

Determining the Presence of NSCLC Genetic Mutations

Biomarker testing is how oncologists identify genetic mutations in non-small cell lung cancer patients. These tests may also be referred to as molecular testing or genomic testing.

Biomarker tests usually involve examining tissue samples collected during a biopsy or surgery by a pathologist in a lab. Another testing approach is known as next-generation sequencing (NGS), which explores a variety of biomarkers at once and requires a blood sample, known as a liquid biopsy.

Advances in NSCLC Treatments Make It Possible to Target Genetic Mutations

The results of lung cancer biomarker testing allow the cancer care team to identify available drugs that will “target” the specific genetic mutations. Targeted therapy drugs stop or slow the growth of cells with a specific genetic mutation. Different drugs are used for different mutations. If no mutations are found, the oncology team will use other types of cancer treatments for the patient based on proven clinical pathways most likely to give the patient the best results.

Targeted therapy for non-small cell lung cancer is available to patients with stage IV (four) lung cancer or those whose NSCLC has returned. Researchers are extensively studying how these treatments can be incorporated earlier in the treatment plans for NSCLC patients.

Common targeted therapy treatment approaches for non-small cell lung cancer based on genetic mutations include:

  • ALK-positive and EGFR-positive lung cancer can be treated with targeted therapy pills called tyrosine kinase inhibitors (TKIs). While these drugs can control the cancer for months or even years, they cannot cure lung cancer.

  • BRAF-positive lung cancer can be treated with a combination of targeted therapies or an immunotherapy and chemotherapy combination.

  • KRAS mutation may allow patients to receive other first-line treatments, including surgery, radiation, chemotherapy, or immunotherapy. If these treatments are ineffective, a KRAS inhibitor targeted therapy can be used for about half of patients.

Extensive research and development are underway for new drugs and treatments that can target various genetic mutations associated with lung cancer. To slow down the growth of lung cancer, most patients receive other therapies along with targeted therapy, such as chemotherapy and/or radiation therapy.

Your doctor will determine your best lung cancer treatment plan based on several factors, help you identify treatment options based on your unique case, and develop a personalized medication based on genetic mutations of lung cancer.


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Personalized Lung Cancer Care Based on Genetic Mutations is Available in Brevard County, Florida

At Cancer Care Centers of Brevard, we offer our patients personalized cancer care using the latest biomarker testing to develop a personalized lung cancer treatment plan. If you live in the Brevard County area, request a consultation at one of our cancer centers in Palm Bay, Melbourne, Merritt Island, or Rockledge. We also provide access to clinical trials through our Brevard County locations.