Table 1. Open in new tab Potentially...

Pathway alterations

Frequency

Targeted therapies

Status of inhibitors

MAPK pathway alterations

NF1 or SPRED1 bi-allelic loss without RAS, RAF, or KIT mutation

15.8%

MEK inhibitors

Approved for other cancer indications

KIT mutation without bi-allelic loss of NF1 or SPRED1

7.9%

KIT inhibitors

Approved for other cancer indications

KIT mutation with bi-allelic loss of NF1 or SPRED1

5.9%

KIT and/or MEK inhibitors

Approved for other cancer indications

Non-V600E BRAF mutation

5.0%

BRAF and MEK inhibitors

In clinical use, durable responses in a minority of patients

Receptor tyrosine kinase fusion

4.0%

RTK inhibitors (ALK, NTRK inhibitors)

Approved for other cancer indications

BRAF fusion

3.0%

Type IIa BRAF inhibitors and/or MEK inhibitors

Approved for other cancer indications

Protein kinase C fusion

1.0%

PKC inhibitors

Investigational

Other alterations

CDK4/6 or CCND1/CCND2 amplification, p16 loss

67.3%

CDK4/6 inhibitors

Approved for other cancer indications

PAK1 or YAP1 amplification

29.7%

Verteporfin

Approved for other indications

MDM2 amplification

12.9%

MDM2 inhibitors

Investigational

ATM loss of function

6.9%

PARP inhibitors

Approved for other indications

Table 1.

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Potentially actionable alterations in acral melanomas without BRAF^V600E mutation

Pathway alterations	Frequency	Targeted therapies	Status of inhibitors
MAPK pathway alterations
NF1 or SPRED1 bi-allelic loss without RAS, RAF, or KIT mutation	15.8%	MEK inhibitors	Approved for other cancer indications
KIT mutation without bi-allelic loss of NF1 or SPRED1	7.9%	KIT inhibitors	Approved for other cancer indications
KIT mutation with bi-allelic loss of NF1 or SPRED1	5.9%	KIT and/or MEK inhibitors	Approved for other cancer indications
Non-V600E BRAF mutation	5.0%	BRAF and MEK inhibitors	In clinical use, durable responses in a minority of patients
Receptor tyrosine kinase fusion	4.0%	RTK inhibitors (ALK, NTRK inhibitors)	Approved for other cancer indications
BRAF fusion	3.0%	Type IIa BRAF inhibitors and/or MEK inhibitors	Approved for other cancer indications
Protein kinase C fusion	1.0%	PKC inhibitors	Investigational
Other alterations
CDK4/6 or CCND1/CCND2 amplification, p16 loss	67.3%	CDK4/6 inhibitors	Approved for other cancer indications
PAK1 or YAP1 amplification	29.7%	Verteporfin	Approved for other indications
MDM2 amplification	12.9%	MDM2 inhibitors	Investigational
ATM loss of function	6.9%	PARP inhibitors	Approved for other indications

Pathway alterations	Frequency	Targeted therapies	Status of inhibitors
MAPK pathway alterations
NF1 or SPRED1 bi-allelic loss without RAS, RAF, or KIT mutation	15.8%	MEK inhibitors	Approved for other cancer indications
KIT mutation without bi-allelic loss of NF1 or SPRED1	7.9%	KIT inhibitors	Approved for other cancer indications
KIT mutation with bi-allelic loss of NF1 or SPRED1	5.9%	KIT and/or MEK inhibitors	Approved for other cancer indications
Non-V600E BRAF mutation	5.0%	BRAF and MEK inhibitors	In clinical use, durable responses in a minority of patients
Receptor tyrosine kinase fusion	4.0%	RTK inhibitors (ALK, NTRK inhibitors)	Approved for other cancer indications
BRAF fusion	3.0%	Type IIa BRAF inhibitors and/or MEK inhibitors	Approved for other cancer indications
Protein kinase C fusion	1.0%	PKC inhibitors	Investigational
Other alterations
CDK4/6 or CCND1/CCND2 amplification, p16 loss	67.3%	CDK4/6 inhibitors	Approved for other cancer indications
PAK1 or YAP1 amplification	29.7%	Verteporfin	Approved for other indications
MDM2 amplification	12.9%	MDM2 inhibitors	Investigational
ATM loss of function	6.9%	PARP inhibitors	Approved for other indications

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