Table 2.

A list of actionable genes, the alteration types, and the alteration frequencies for several common cancer types.

Tumor type	Actionable genes	Alteration type	Frequency	Comments
Non-small cell lung cancer	BRAF	Mutations	5–10%
	DDR2	Mutations	1–6%
	EGFR	Mutations	4–18%
	EML4-ALK	Fusion	4%
	ERBB2	Mutations	2–3%
	FGFR1	Amplification	2–17%
	FGFR3	Fusion	2%
	KRAS	Mutations	1–32%	1% in adenocarcinoma, 32% in squamous cell carcinoma
	MAP2K1	Mutations	1%
	MET	Amplification	1–4%
	MET	Mutations	3–8%	3% MET exon 14 mutation in lung adenocarcinoma
	NF1	Mutations	11%
	NTRK1	Fusion	2–4%
	PIK3CA	Mutations	4–16%
	PTEN	Mutations/Deletion	1–8%
	RET	Fusion	2–4%
	RICTOR	Amplification	2–5%
	ROS1	Fusion	4–11%
	STK11	Mutations	2–17%
Bladder	AKT1	Mutations	3%
	CDKN2A	Deletion	47%
	CDKN2A	Mutations	5%
	EGFR	Amplification	11%
	ERBB2	Amplification	7%
	ERBB3	Mutations	11%
	FGFR3	Mutations	45%	60–80% in non-muscle-invasive; 15–20% in muscle-invasive bladder cancer
	FGFR3	Amplification	3%
	FGFR3-TACC3	Fusion	5%
	KRAS	Mutations	4%
	MDM2	Amplification	9%
	PIK3CA	Mutations	20%
	PTEN	Mutations	3%
	PTEN	Deletion	13%
	TSC1	Mutations	9%
Biliary	BRAF	Mutations	7%
	EGFR	Mutations/Amplification	5%
	ERBB2	Mutations/Amplification	4–18%	18% in gallbladder carcinoma
	FGF19	Amplification	3%
	FGFR1	Mutations/Amplification	4%
	FGFR2	Fusion	5%	5% in intrahepatic cholangiocarcinoma
	IDH1/2	Mutations	0–6%	4–6% in intrahepatic cholangiocarcinoma
	KRAS	Mutations	18%
	MDM2	Amplification	5%
	PIK3CA	Mutations	7%
	PTEN	Deletion	1–7%	7% in gallbladder carcinoma
Gastric	EGFR	Mutations	3–5%
	EGFR	Amplification	6%
	ERBB2	Mutations	5–7%
	ERBB2	Amplification	13%
	ERBB3	Mutations	5–11%
	ERBB3	Amplification	4%
	FGFR1	Mutations	4%
	FGFR2	Amplification	5%
	KRAS	Mutations	6%
	MET	Mutations	2%
	MET	Amplification	4%
	PIK3CA	Mutations/Amplification	24%	42% and 72% in MSI-H and EBV+ gastric cancer, respectively
	PTEN	Mutations	4–8%
	PTEN	Deletion	4%
Melanoma	BRAF	Mutations	45%
	CDKN2A	Deletion	13%
	IDH1	Mutations	6%
	KDR	Amplification	3%
	KIT	Amplification	4%
	MAP2K1	Mutations	5%
	NF1	Mutations	14%
	NRAS	Mutations	10–25%
	PDGFRA	Amplification	3%
Breast	11q	Amplification	15%
	AKT1	Mutations	2–4%
	CDKN2A	Deletion	3–4%
	ERBB2	Mutations/Amplification	13%
	ESR1	Mutations	10%	ER+ breast cancer, metastatic samples and not primary (marker of resistance to antiestrogen therapy)
	FGFR1	Amplification	10–15%
	FGFR2	Amplification	4%
	MAP2K4	Mutations	2–7%
	MAP3K1	Mutations	4–13%
	NF1	Mutations	2–4%
	NTRK3	Fusion	92%	Secretory breast cancer
	PIK3CA	Mutations	9–45%
	PIK3CA	Amplification	4–5%
	PIK3R1	Mutations	2%
	PTEN	Mutations/Deletion	3–8%
	RB1	Mutations/Deletion	5–6%	Marker of resistance to CDK 4/6 inhibitors
Colorectal	AKT1	Mutations	1–6%
	BRAF	Mutations	3–47%	47% in MSI-H colorectal cancer
	ERBB2	Mutations/Amplification	6–13%
	ERBB3	Mutations	4–20%
	KRAS	Mutations	35%
	NRAS	Mutations	10%
	PIK3CA	Mutations	15–37%	37% MSI-H colorectal cancer
	PIK3R1	Mutations	2–17%
	PTEN	Deletion	4–20%	20% MSI-H colorectal cancer
Ovarian	AKT1	Amplification	3%
	AKT2	Amplification	2%
	BRAF	Mutations	2–6% (low grade serous ovary)	Extremely rare in high grade ovarian cancer; 2–6% low grade serous ovarian cancer (excluding borderline tumors)
	BRCA1 (germline or somatic)	Mutations	9%
	BRCA2 (germline or somatic)	Mutations	5%
	CCND1	Amplification	20%
	CDKN2A	Deletion	32%
	FGFR1	Amplification	5%
	KRAS	Mutations/Amplification	19–33% (low grade serous ovary)	Extremely rare in high grade; 19–33% low grade serous ovarian cancer (excluding borderline tumors)
	NF1	Mutations/Deletion	12%
	NOTCH3	Mutations/Amplification	11%
	PIK3CA	Mutations/Amplification	18%
	PTEN	Mutations/Deletion	7%
Glioblastoma	BRAF	Mutations	2%
	CDK4	Amplification	14%
	CDK6	Amplification	2%
	CDKN2A/B	Deletion	61%
	EGFR	Mutations	17–21%
	EGFR	Amplification	41–44%
	FGFR1-TACC1	Fusion	NA
	FGFR3-TACC3	Fusion	3–7%
	IDH1	Mutations	5–12%
	MDM2	Amplification	7%
	MDM4	Amplification	8%
	MET	Amplification	2%
	NF1	Mutations	10%
	NTRK1	Fusion	1%
	PDGFRA	Amplification	10%
	PIK3CA	Mutations/Amplification	25%
	PTEN	Mutations/Deletion	41%

MSI-H = Microsatellite instability high; EBV = Epstein-Barr Virus