Table 1.

Incidence, method of detection, and known secondary mutation in selected driver mutations.

Driver mutation	Histology of NSCLC	Incidence	Method of detection	Secondary mutation
BRAF V600E non-V600E	Adenocarcinoma	1–2% 1–2%	DNA sequencinga	Unknown
EGFR exon 20	Adenocarcinoma	4–19%	DNA sequencing	Unknown
FGFR FGFR1 amplification FGFR2–4 mutation gene fusion/translocation	Squamous Adenocarcinoma Squamous Squamous Adenocarcinoma	25% 2–3% 2–3% 0.3–3.5% 0.5%	FISH or RNA NGSb DNA sequencing FISH or RNA NGS or possibly IHCc	Unknown Unknown Unknown
Her-2 Exon 20 Amplification overexpression	Adenocarcinoma Adenocarcinoma Adenocarcinoma	2–9% 1–2% Not reported	DNA sequencing FISH or RNA NGS or possibly IHC IHC	Unknown Loss of extracellular domain Unknown
K-RAS Mutation	Adenocarcinoma	20–30%	DNA sequencing	Unknown
MET METex14 mutation MET amplification	Adenocarcinoma, particularly sarcomatoid subtype Adenocarcinoma	3–4% 2–4%	DNA sequencing or possibly IHC DNA sequencing, FISH or IHC	Y1230C mutation WT KRAS amplification Unknown
NGR1 gene fusion/translocation	Adenocarcinoma	0.2–0.8%	FISH or RNA NGS, possibly IHC	Unknown
NTRK gene fusion/translocation mutation	Adenocarcinoma Large cell neuroendocrine	NTRK1: 3.5% NTRK2: 0.2–1% NTRK3: <1% NTRK 2 or 3: 10%	FISH or RNA NGS or possibly IHC DNA sequencing	Gatekeeper and solvent front mutation Unknown
PI3K pathway pTEN protein loss PI3K amplification PI3K mutation pTEN R233* mutation AKT1	Adenocarcinoma and squamous Adenocarcinoma and squamous Adenocarcinoma and squamous Adenocarcinoma and squamousAdenocarcinoma and squamous	75% and 33% 6.2% 4% 4–7% 1%	IHC FISH or RNA NGS DNA sequencing DNA sequencing DNA sequencing	Unknown Unknown Unknown Unknown Unknown
RET gene fusion/translocation	Adenocarcinoma	1–2%	FISH or RNA NGS or possibly IHC	Gatekeeper or solvent front mutation Bypass pathway activation
ROS1 gene fusion/translocation	Adenocarcinoma	1–2%	FISH or RNA NGS or IHC	Gatekeeper or solvent front mutation Bypass pathway activation

^aDNA sequencing includes direct sequencing, hot spot sequencing and DNA NGS.

^bRNA sequencing using NGS.

^cValidation study of the sensitivity and specificity of IHC relative to FISH or NGS for NTRK fusion and RET fusion are ongoing.

FISH, fluorescence in situ hybridization; IHC, immunohistochemistry; NGS, next-generation sequencing; NSCLC, non-small cell lung cancer; WT, wild type.