Melanocytic Lesions

Table 1. Rates of gains and losses significantly higher than 5% for specific chromosome regions in primary melanoma of all subtypes combined (Literature Review). The is a list of significantly gains and losses selected and evaluated based on a systematic literature search performed on 235 peer-reviewed manuscripts focusing on findings of copy number abnormalities in melanocytic lesions published between 1998 and 2022. Table derived from Barron et al., 2026 [PMID 41898865] with permission from Cancer Genetics. All p-values in the listed CNAs were ≤0.05 and were considered indicative of significance. The abnormalities were reported by at least 3 manuscripts. Possible genes affected by the gain or loss are listed.

Event Type	Region	Rate of Gain or Loss (%)	Possible Genes Affected
Gain	1p12	12	NOTCH2 ***, ADAM30 ***
	1p13	9	NRAS *
	1q	26
	1q21	16	PDE4DIP ***, BCL9 *, S100A9 ***, S100A10 ***, S100A11 ***, S100A12 ***
	1q23	28	NTRK1 *, KIRREL ***
	1q32	41	MDM4 *
	2q31	14	PDE11A ***
	3p13	10	MITF *
	4p	10
	4q12	17	KIT *, KDR *, PDGFRA *
	5p	14
	5p15	32	TERT *
	5q	10
	6p	30
	6p25	58	RREB1 *
	6p21	25	CCND3 *
	6q14	34	PHIP ***
	7p	23
	7p11	17	EGFR *
	7q	27
	7q31	26	MET *
	7q34	27	BRAF *
	8p	6
	8q	50
	8q24	39	MYC *
	11p15	15	HRAS *
	11q	8
	11q13	27	CCND1 *
	11q14	11	GAB2 *
	12p12	8	KRAS *, PIK3C2G ***
	12q14	21	CDK4 *
	12q15	11	HDM2/MDM2 *
	13q14	10	RB1 **
	14q32	37	AKT1 *
	15q	14
	17p13	18	TP53 **
	17q	18
	17q11	15	NF1 **
	17q24	32	BPTF ***, PRKCA *, PRKAR1A **
	19p13	37	MAP2K2 *
	20p11	11
	20q	23
	20q13	22	MYBL2 *, ZNF217 *, CYP24 ***, STK6 *, P-REX1 *, SS18L1 ***, GNAS *, SNAI1 *, SNAI2 *
	21q	14
	22q13	21	MKL1 ***, EP300 ***
Loss	1p	23
	1p36	32	PRDM16 ***, ARID1A **
	3p21 a	15	BAP1 **
	3q	14
	4q	10
	5q	22
	6q	14
	6q23	29	MYB ***
	6q25 b	44	ARID1B **
	8p	9
	9p	32
	9p21	38	CDKN2A **
	9p24	10	CD274 ***, JAK2 ***, PTPRD **
	9q	29
	9q12	13
	10p	19
	10p15	14	PRKCQ ***, NET1 ***, KLF6 **, IL15RA ***, CALML5 ***, LARP4B ***
	10q	34
	10q23	25	PTEN **
	11p11	23	CD82 **
	11q	18
	11q22	9	YAP1 ***
	11q24	26	ETS1 ***, CHEK1 ***
	13q14	8	RB1 **
	16p	14
	16q	25
	16q23	13	BANP **, CBFA2T3 **, FANCA **, CDK10 ***
	17p	21
	17p13	12	TP53 **
	18q	9
	20p11	18
	20q11	20	E2F1 ***

*Oncogene; **Tumor suppressor gene; ***Other/complex (context-dependent function, dual role, limited melanoma-specific evidence, or gene located within amplified locus without definitive driver status)

Table 2. Rates in percentage of CNAs commonly tested on FISH panels across different melanoma subtypes. Values in red represent rates calculated from <25 reported cases. The number of reported cases appears in parentheses (). The symbol “-” designates data not available.

Melanoma Subtype	Rate of Gain of 6p25	Rate of Loss of 6q23	Rate of Gain of 8q24	Rate of Loss of 9p21	Rate of Gain of 11q13
General cutaneous	58 (644)	38 (515)	33 (567)	52 (880)	25 (1871)
Acral	72 (149)	42 (171)	47 (79)	28 (222)	39 (515)
Blue nevus like	83 (23)	61 (23)	-	-	50 (18)
Desmoplastic	44 (16)	33 (3)	-	-	31 (16)
Mucosal	97 (33)	80 (20)	75 (24)	39 (233)	17 (260)
Nevoid	66 (41)	15 (41)	31 (13)	69 (13)	24 (41)
Spitzoid/Spitz	54 (99)	33 (141)	-	39 (134)	33 (146)
Uveal	-	33 (40)	58 (249)	-	0 (83)

Table 3. Rates of abnormalities detected by FISH panels for each melanoma subtype and 95% confidence intervals for the given rates. The number of cases on which the rates are based is given.

Melanoma Subtype	Rate of FISH Abnormality Detected (%)	Lower 95% Confidence Limit	Upper 95% Confidence Limit	Number of Cases
General cutaneous	82	80	84	1682
Acral	88	81	92	153
Blue nevus like	94	68	100	16
Mucosal	100	86	100	30
Nevoid	93	85	98	75
Spitzoid/Spitz	70	62	77	169

Table 4. The percentage of melanomas with greater than 3 CNAs reported by CMA for each melanoma subtype and the 95% confidence lower bound for the proportion in the given number of reported cases.

Melanoma Subtype	Percentage of Cases with >3 CNAs by CMA (%)	Lower 95% Confidence Limit	Number of Cases
Overall	94		769
General cutaneous	94	92	579
Acral	100	96	83
Blue nevus like	80	64	30
Desmoplastic	86	61	14
Mucosal	95	76	19
Nevoid	85	58	13
Spitzoid/Spitz	67	16	3
Uveal	100	88	28