Table 1.
Summarizes the most common genetic mutations in lung cancer and how they are commonly screened for in current clinical practice.
Genes | Common Mutations | Mutation Prevalence | Screening Protocol |
---|---|---|---|
EGFR [5,6] | Exon 19 deletion * Exon 20 T790M Exon 21 L858R * (*: Present in 40% of patients) |
Adenocarcinoma: 38% Non-adenocarcinoma: 12% Western: 10–15% Asia: 30–40% African-American: 20% Male: 24% Female: 44% |
Direct DNA sequencing is the gold standard if sample is more than 50% tumor content. If not, PCR preferred. |
MET [7,8,9,10] |
TPR-MET fusion Exon 14 skip c-MET-N375S |
Adenosquamous carcinoma: 5% Adenocarcinoma: 3% Squamous cell carcinoma: 2% Western: 12% Asian: 1–4% African-American: 10% |
FISH assay is the gold standard; next-generation sequencing is reliable only for a high-level of MET gene amplification. |
ALK [11,12] | Fusion with: -TMP3-TFG-CLTCL1 -ATIC-EML4 * (*: Most common, ~30% of all ALK fusions) |
Adenocarcinoma: 5% Western: 5% Asian: 5% |
FISH assay is the gold stand; RT-PCR is also FDA-approved for only EML4-ALK fusion. |
RET [13] |
RET-KIF5B fusion * RET-CCDC6 fusion RET-NCOA4 fusion (*: Detected in EGFR inhibitor resistant cancers) |
All NSCLC: 1.5% Adenocarcinoma: 1.7% Age > 60: 2.0% Age < 60: 1.0% Male: 0.9% Female: 1.7% |
Next-generation sequencing and FISH assays are comparable; however, FISH demonstrated lower sensitivity for RET-NCOA4 fusions |
HER2 [14] | Exon 20 12 bp insertion Exon 20 L755S Exon 20 G776C |
Adenocarcinoma: 2–4% | Mutation: next-generation sequencing, Amplification: FISH, Overexpression: IHC. |