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; open access]. 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 **
	3p21a	15	BAP1 **
	3q	14
	4q	10
	5q	22
	6q	14
	6q23	29	MYB ***
	6q25b	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)

^aMay be inconsequential in melanocytic proliferations with Spitzoid morphology; ^bReported only in mucosal melanomas

Table 2. Rates in percentage of copy number abnormalities commonly tested on FISH panels across different melanoma subtypes.* Table derived from Barron et al., 2026 [PMID 41898865; open access].

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)

*The symbol “-” designates data not available; The number of reported cases appears in parentheses ().

Table 3. Rates of abnormalities detected by FISH panels for each melanoma subtype and 95% confidence intervals for the given rates.* Table derived from Barron et al., 2026 [PMID 41898865; open access].

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

*The number of cases on which the rates are based is given.

Table 4. The percentage of melanomas with greater than 3 copy number abnormalities (CNAs) reported by chromosomal microarray (CMA) for each melanoma subtype and the 95% confidence lower bound for the proportion in the given number of reported cases. Table derived from Barron et al., 2026 [PMID 41898865; open access].

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

Table 5. Rates of chromosomal abnormalities detected in primary uveal melanoma associated with high risk of metastasis and aggressive clinical behavior. Table derived from Barron et al., 2026 [PMID 41898865; open access].

Chromosome	Region	Abnormality	Rate of Abnormality (%)
1	1p	loss	27
1	1p36	loss	34
1	1q	gain	11
3	whole	loss	49
3	partial	loss	8
6	6q	loss	22
8	whole	gain	39
8	8p	loss	16
8	8p	gain	13
8	8q	gain	52
8	8q	isochromosome	23
8	8q24	gain	58
16	16q	loss	25
3, 8	3 whole, 8q	monosomy 3, gain 8q	43

Table 6. Comparison of rates of abnormalities reported in Spitzoid lesions in three or more manuscripts.* Table derived from Barron et al., 2026 [PMID 41898865; open access].

Region	Abnormality	Gene Affected	Spitz Nevus (%)	Spitz Melanocytoma (%)	Spitzoid/Spitz Melanoma (%)	Number of Manuscripts
6p25	gain	RREB1	3	9	54	13
6q23	loss	MYB	0	11	33	10
7q	gain	BRAF	2	67	21	3
8q	gain	MYC	-	3	4	3
9p21	loss	CDKN2A	2	18	39	21
11p15	gain	HRAS	19	0	4	10
11q13	gain	CCND1	0	6	33	11
FISH	at least 1 CNA	several	14	18	70	25
CMA	>3 CNAs	many	2	16	67	6

*The symbol “-” designates data not available

Table 7. CNAs reported in at least 3 manuscripts in at least 50 cases of primary melanomas and 50 cases of metastases with significant difference in rates (P-values given for differences).* Individual P-values indicate whether each abnormality is significantly greater than 5%. Rates in bold were the greater of the comparison between primary and metastatic melanomas. Table derived from Barron et al., 2026 [PMID 41898865; open access].

Region	Abnormality	Genes Affected	Rate in Primary (%)	P-value Primary (P)	Rate in Metastasis (%)	P-value Metastasis	P-value Difference	Number of Primary Melanoma Cases	Number of Metastasis Cases
3p13	gain	MITF	10	<0.001	19	<0.001	0.009	255	214
5p15	gain	TERT, NKD2	28	<0.001	12	0.002	0.005	162	97
6q	loss	-	27	<0.001	50	<0.001	0.001	271	68
chr7	polysomy	-	25	<0.001	57	<0.001	<0.001	651	137
7p11	gain	EGFR	17	<0.001	34	<0.001	<0.001	231	213
7q31	gain	MET, CAV1, others	32	<0.001	17	<0.001	<0.001	348	195
7q34	gain	BRAF	30	<0.001	58	<0.001	<0.001	381	142
8q24	gain	MYC	33	<0.001	21	<0.001	0.008	567	160
11q	loss	-	24	<0.001	40	<0.001	0.014	225	68
11q13	gain	CCND1	25	<0.001	17	<0.001	<0.001	1629	379
12q14	gain	CDK4	31	<0.001	7	0.408	<0.001	322	129
19p13	gain	MAP2K2	44	<0.001	4	1	<0.001	137	69

*The symbol “-” designates data not available

Table 8. FISH probe sets for analysis of melanocytic lesions with published data included in this study. Table derived from Barron et al., 2026 [PMID 41898865; open access].

Chromosomes	Loci	Genes	Number of Probes
6, 11	6p25, 6q23, CEP6, 11q13	RREB1, MYB, CCND1	4
6, 8, 9, 11	6p25, 8q24, 9p21, CEP9, 11q13	RREB1, MYC, CDKN2A, CCND1	5
6, 9, 11	6p25, 6q23, CEP6, 9p21, CEP9, 11q13	RREB1, MYB, CDKN2A, CCND1	6
6, 8, 9, 11	6p25, 6q23, CEP6, 8q24, 9p21, 11q13	RREB1, MYB, MYC, CDKN2A, CCND1	6
6, 8, 9, 11	6p25, 6q23, 8q24, 8p11.1, 9p21, 9q21.2, 11q13, 11p15.5	RREB1, MYB, MYC, POETA, CDKN2A, GNAQ, CCND1, HRAS	8

Table 9. Genes classified as other/complex in Table 1. Table derived from Barron et al., 2026 [PMID 41898865; open access].

Gene	Function / Potential Role
ADAM30	Limited functional evidence supporting a driver role in melanoma
BPTF	Chromatin remodeler with context-dependent oncogenic properties
CYP24	Vitamin D metabolism gene; indirect relevance to tumor biology
EP300	Histone acetyltransferase; may function as coactivator or tumor suppressor depending on context
KIRREL	Limited mechanistic validation as melanoma driver
MKL1	Transcriptional coactivator; context-dependent oncogenic activity
NOTCH2	Context-dependent signaling with oncogenic and tumor-suppressive roles depending on cellular context
PDE11A	Phosphodiesterase with unclear contribution to melanoma progression
PDE4DIP	Scaffold protein; no consistent evidence of recurrent oncogenic activation in melanoma
PHIP	Implicated in melanoma progression but mechanistically complex and not a canonical oncogene
PIK3C2G	PIK3 family member; limited evidence of recurrent activating alterations in melanoma
S100A9, S100A10, S100A11, S100A12	Inflammatory mediators more commonly implicated in tumor microenvironment modulation than as primary genomic drivers
SS18L1	Transcriptional regulator without clear melanoma driver validation
CALML5	Calcium-binding protein; limited oncogenic validation
CD274 (PD-L1)	Immune checkpoint regulator; deletion effects are context-dependent
CDK10	Cell-cycle regulator; limited melanoma-specific driver evidence
CHEK1	DNA damage response kinase; dual context-dependent role
ETS1	Transcription factor with context-dependent oncogenic properties
IL15RA	Immune regulatory receptor; indirect tumor role
JAK2	Oncogenic kinase; loss not typical driver event in melanoma
LARP4B	RNA-binding protein; insufficient evidence as melanoma driver
MYB	Canonical oncogene; loss does not represent typical driver mechanism in melanoma
NET1	RhoA GEF; limited melanoma-specific evidence
PRDM16	Context-dependent transcriptional regulator; not established as recurrent melanoma tumor suppressor
PRKCQ	Kinase with signaling roles; melanoma-specific driver role unclear
YAP1	Hippo pathway oncogene; deletion suggests complex regional effects