Genetic Abnormalities

All cells have coded instructions in their genes. When changes occur to the genes, the cells change their normal behavior. Changes in the genes can cause normal cells to become cancer cells. Genetic changes can be inherited, but in the case of lung cancer, the genetic changes that cause cancer to develop can be caused by other factors, such as environmental exposure to pollutants like tobacco smoke. The most common cause of lung cancer is tobacco smoking.1,2

Each cancer is unique with different genetic changes, and as the cancer grows, additional changes occur in the genes. Scientists have found that there are certain changes, or mutations, that commonly occur in many types of cancers. These mutations are often a target for potential treatments to stop the cancer and can be identified through biomarker testing.1

In non-small cell lung cancer (NSCLC), researchers have identified several genetic mutations that are known to play critical roles in the development and progression of the disease.

Epidermal Growth Factor Receptor (EGFR)

An estimated 10 percent of patients with NSCLC in the United States have a mutation associated with the epidermal growth factor receptor (EGFR). The EGFR gene is responsible for a protein that helps a cell respond to its environment and can trigger cell growth, division, and survival. The EGFR mutations are most often found in tumors in female patients who have never smoked (patients are considered “never smokers” if they have smoked less than 100 cigarettes in their lifetime). The tumors are likely to be adenocarcinoma. However, EGFR mutations are not exclusive to this type of NSCLC or non-smokers – mutations have also been found in smokers and in other tumor types.1,3


Approximately 15-25 percent of patients with NSCLC adenocarcinomas have mutations on the KRAS gene. The KRAS gene is involved in regulating cell division and cell death, and mutations on this gene have been implicated in the development of several cancers. KRAS mutations are found in tumors among both smokers and non-smokers.1,3

Anaplastic Lymphoma Kinase (ALK)

An estimated 3-5 percent of lung tumors have mutations on the anaplastic lymphoma kinase (ALK) gene. The ALK gene provides instructions for a protein that plays an important role in cell growth, division, and maturation. ALK mutations are more common in light smokers (defined as less than 10 pack years*) and/or never-smokers. These mutations are also associated with younger patient age and adenocarcinomas.3,4

Other Genetic Abnormalities in NSCLC

In addition to EGFR, KRAS and ALK mutations, scientists have found several additional genetic abnormalities that can occur in NSCLC, including:

  • AKT1
  • BRAF
  • DDR2
  • HER2
  • FGFR1
  • FGFR3
  • MEK1 (also known as MAP2K1)
  • MET
  • NRAS
  • PIK3CA
  • PTEN
  • RET
  • ROS1 3

In many cases, the identification of these genetic mutations has led to the development of targeted therapies to treat lung cancers that display these mutations.4

*Pack years is a term used to help quantify the equivalent of how many years a patient has smoked. It is calculated by multiplying the number of packs of cigarettes smoked per day by the number of years the person has smoked. For example, smoking one pack per day for one year equals 1 pack year, whereas smoking two packs per day for two years equals 4 pack years.

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Written by: Emily Downward | Last reviewed: January 2017.