Damage to the genes can cause normal cells to change and become cancer cells. While genetic changes can be inherited, 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. Each lung cancer is unique with different genetic changes, but scientists have found that there are certain changes, or mutations, that commonly occur in many types of cancers.1 In addition to EGFR, KRAS and ALK, scientists have found several additional genetic abnormalities that can occur in non-small cell lung cancer (NSCLC), including:
AKT1
Found in approximately 1 percent of all NSCLC, mutations on the AKT1 gene affect both adenocarcinomas and squamous cell carcinomas.
BRAF
Mutations on the BRAF gene have been found in 1-4 percent of all NSCLC and most often occurs in adenocarcinomas.
DDR2
Approximately 2.5-3.8 percent of lung squamous cell carcinomas and 4 percent of lung adenocarcinomas have a mutation on the DDR2 gene.
HER2
Mutations on the HER2 gene are found in 2-4 percent of all NSCLC. These mutations are more commonly found in never smokers with adenocarcinomas.
FGFR1
FGFR1 mutations are mainly found in squamous cell lung cancers, with approximately 20 percent of squamous cell lung cancers having the mutation.
FGFR3
Several different FGFR3 mutations have been identified in lung cancer. Each of the mutations on this gene is rare, found in 0.5 percent to 2.0 percent of NSCLC.
MEK1 (also known as MAP2K1)
Approximately 1 percent of all NSCLC have mutations on the MEK1 gene. These mutations are more common in adenocarcinomas.
MET
Researchers have found multiple mechanisms of MET activation in NSCLC, and overexpression of MET protein is found in 25-75 percent of NSCLC.
NRAS
Mutations on the NRAS gene have been found in approximately 1 percent of all NSCLC and are more common in adenocarcinomas.
NTRK1
NTRK1 mutations are found in approximately 3.3 percent of lung adenocarcinomas.
PIK3CA
Approximately 1-3 percent of all NSCLC have mutations on the PIK3CA gene. These mutations are more commonly found in squamous cell lung cancers.
PTEN
Mutations on the PTEN gene have been found in 4-8 percent of all NSCLC, most often in squamous cell lung cancers.
RET
Approximately 1.3 percent of lung cancers have RET mutations. These mutations occur almost entirely in adenocarcinomas.
RICTOR
Approximately 10.9-14.3 percent of lung adenocarcinomas and 10.6-16.9 percent of squamous cell lung cancers show a mutation on the RICTOR gene.
ROS1
Mutations on the ROS1 gene are present in approximately 2 percent of NSCLC, most commonly in patients who are light smokers or never-smokers.2
Scientists search to identify genetic mutations such as these for several reasons. Genetic changes may be associated with particular patterns of growth or different responsiveness to certain types of treatment (how effective the treatment will be against the cancer). For some specific genetic mutations, doctors have found targeted therapies to treat tumors that display the mutation. Targeted therapies are currently the focus of much research in lung cancer treatment.1,3