Melanocytic Lesions: Difference between revisions

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'''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 Barren et al., 2026 [<nowiki>PMID 41898865</nowiki><ref>{{Cite journal|last=Reyes Barron|first=Cynthia|last2=Geiersbach|first2=Katherine B.|last3=Alomari|first3=Ahmed K.|last4=Deak|first4=Kristen L.|last5=Golem|first5=Shivani|last6=Williams|first6=Eli S.|last7=Aypar|first7=Umut|last8=Zou|first8=Ying S.|last9=Wei|first9=Lei|date=2026-03-18|title=Clinical Utility of Copy Number Abnormality Analysis in the Evaluation of Melanocytic Lesions for Diagnosis and Prognosis: An Evidence-Based Review from the Cancer Genomics Consortium Working Group for Melanocytic Lesions|url=https://pubmed.ncbi.nlm.nih.gov/41898865|journal=Genes|volume=17|issue=3|pages=331|doi=10.3390/genes17030331|issn=2073-4425|pmc=13026022|pmid=41898865}}</ref>] 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.
'''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 [<nowiki>PMID 41898865</nowiki><ref name=":0">{{Cite journal|last=Reyes Barron|first=Cynthia|last2=Geiersbach|first2=Katherine B.|last3=Alomari|first3=Ahmed K.|last4=Deak|first4=Kristen L.|last5=Golem|first5=Shivani|last6=Williams|first6=Eli S.|last7=Aypar|first7=Umut|last8=Zou|first8=Ying S.|last9=Wei|first9=Lei|date=2026-03-18|title=Clinical Utility of Copy Number Abnormality Analysis in the Evaluation of Melanocytic Lesions for Diagnosis and Prognosis: An Evidence-Based Review from the Cancer Genomics Consortium Working Group for Melanocytic Lesions|url=https://pubmed.ncbi.nlm.nih.gov/41898865|journal=Genes|volume=17|issue=3|pages=331|doi=10.3390/genes17030331|issn=2073-4425|pmc=13026022|pmid=41898865}}</ref>; 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.
{| class="wikitable"
{| class="wikitable"
|+
|+
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|1p12
|1p12
|12
|12
|NOTCH2 ***, ADAM30 ***
|''NOTCH2'' ***, ''ADAM30'' ***
|-
|-
|1p13
|1p13
|9
|9
|NRAS *
|''NRAS'' *
|-
|-
|1q
|1q
Line 22: Line 22:
|1q21
|1q21
|16
|16
|PDE4DIP ***, BCL9 *, S100A9 ***, S100A10 ***, S100A11 ***, S100A12 ***
|''PDE4DIP'' ***, ''BCL9'' *, ''S100A9'' ***, ''S100A10'' ***, ''S100A11'' ***, ''S100A12'' ***
|-
|-
|1q23
|1q23
|28
|28
|NTRK1 *, KIRREL ***
|''NTRK1'' *, ''KIRREL'' ***
|-
|-
|1q32
|1q32
|41
|41
|MDM4 *
|''MDM4'' *
|-
|-
|2q31
|2q31
|14
|14
|PDE11A ***
|''PDE11A'' ***
|-
|-
|3p13
|3p13
|10
|10
|MITF *
|''MITF'' *
|-
|-
|4p
|4p
Line 46: Line 46:
|4q12
|4q12
|17
|17
|KIT *, KDR *, PDGFRA *
|''KIT'' *, ''KDR'' *, ''PDGFRA'' *
|-
|-
|5p
|5p
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|5p15
|5p15
|32
|32
|TERT *
|''TERT'' *
|-
|-
|5q
|5q
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|6p25
|6p25
|58
|58
|RREB1 *
|''RREB1'' *
|-
|-
|6p21
|6p21
|25
|25
|CCND3 *
|''CCND3'' *
|-
|-
|6q14
|6q14
|34
|34
|PHIP ***
|''PHIP'' ***
|-
|-
|7p
|7p
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|7p11
|7p11
|17
|17
|EGFR *
|''EGFR'' *
|-
|-
|7q
|7q
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|7q31
|7q31
|26
|26
|MET *
|''MET'' *
|-
|-
|7q34
|7q34
|27
|27
|BRAF *
|''BRAF'' *
|-
|-
|8p
|8p
Line 106: Line 106:
|8q24
|8q24
|39
|39
|MYC *
|''MYC'' *
|-
|-
|11p15
|11p15
|15
|15
|HRAS *
|''HRAS'' *
|-
|-
|11q
|11q
Line 118: Line 118:
|11q13
|11q13
|27
|27
|CCND1 *
|''CCND1'' *
|-
|-
|11q14
|11q14
|11
|11
|GAB2 *
|''GAB2'' *
|-
|-
|12p12
|12p12
|8
|8
|KRAS *, PIK3C2G ***
|''KRAS'' *, ''PIK3C2G'' ***
|-
|-
|12q14
|12q14
|21
|21
|CDK4 *
|''CDK4'' *
|-
|-
|12q15
|12q15
|11
|11
|HDM2/MDM2 *
|''HDM2''/''MDM2'' *
|-
|-
|13q14
|13q14
|10
|10
|RB1 **
|''RB1'' **
|-
|-
|14q32
|14q32
|37
|37
|AKT1 *
|''AKT1'' *
|-
|-
|15q
|15q
Line 150: Line 150:
|17p13
|17p13
|18
|18
|TP53 **
|''TP53'' **
|-
|-
|17q
|17q
Line 158: Line 158:
|17q11
|17q11
|15
|15
|NF1 **
|''NF1'' **
|-
|-
|17q24
|17q24
|32
|32
|BPTF ***, PRKCA *, PRKAR1A **
|''BPTF'' ***, ''PRKCA'' *, ''PRKAR1A'' **
|-
|-
|19p13
|19p13
|37
|37
|MAP2K2 *
|''MAP2K2'' *
|-
|-
|20p11
|20p11
Line 178: Line 178:
|20q13
|20q13
|22
|22
|MYBL2 *, ZNF217 *, CYP24 ***, STK6 *, P-REX1 *, SS18L1 ***, GNAS *, SNAI1 *, SNAI2 *
|''MYBL2'' *, ''ZNF217'' *, ''CYP24'' ***, ''STK6'' *, ''P-REX1'' *, ''SS18L1'' ***, ''GNAS'' *, ''SNAI1'' *, ''SNAI2'' *
|-
|-
|21q
|21q
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|22q13
|22q13
|21
|21
|MKL1 ***, EP300 ***
|''MKL1'' ***, ''EP300'' ***
|-
|-
| rowspan="32" |Loss
| rowspan="32" |Loss
Line 195: Line 195:
|1p36
|1p36
|32
|32
|PRDM16 ***, ARID1A **
|''PRDM16'' ***, ''ARID1A'' **
|-
|-
|3p21 a
|3p21<sup>a</sup>
|15
|15
|BAP1 **
|''BAP1'' **
|-
|-
|3q
|3q
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|6q23
|6q23
|29
|29
|MYB ***
|''MYB'' ***
|-
|-
|6q25 b
|6q25<sup>b</sup>
|44
|44
|ARID1B **
|''ARID1B'' **
|-
|-
|8p
|8p
Line 235: Line 235:
|9p21
|9p21
|38
|38
|CDKN2A **
|''CDKN2A'' **
|-
|-
|9p24
|9p24
|10
|10
|CD274 ***, JAK2 ***, PTPRD **
|''CD274'' ***, ''JAK2'' ***, ''PTPRD'' **
|-
|-
|9q
|9q
Line 255: Line 255:
|10p15
|10p15
|14
|14
|PRKCQ ***, NET1 ***, KLF6 **, IL15RA ***, CALML5 ***, LARP4B ***
|''PRKCQ'' ***, ''NET1'' ***, ''KLF6'' **, ''IL15RA'' ***, ''CALML5'' ***, ''LARP4B'' ***
|-
|-
|10q
|10q
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|10q23
|10q23
|25
|25
|PTEN **
|''PTEN'' **
|-
|-
|11p11
|11p11
|23
|23
|CD82 **
|''CD82'' **
|-
|-
|11q
|11q
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|11q22
|11q22
|9
|9
|YAP1 ***
|''YAP1'' ***
|-
|-
|11q24
|11q24
|26
|26
|ETS1 ***, CHEK1 ***
|''ETS1'' ***, ''CHEK1'' ***
|-
|-
|13q14
|13q14
|8
|8
|RB1 **
|''RB1'' **
|-
|-
|16p
|16p
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|16q23
|16q23
|13
|13
|BANP **, CBFA2T3 **, FANCA **, CDK10 ***
|''BANP'' **, ''CBFA2T3'' **, ''FANCA'' **, ''CDK10'' ***
|-
|-
|17p
|17p
Line 303: Line 303:
|17p13
|17p13
|12
|12
|TP53 **
|''TP53'' **
|-
|-
|18q
|18q
Line 315: Line 315:
|20q11
|20q11
|20
|20
|E2F1 ***
|''E2F1'' ***
|}
|}
'''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.
<nowiki>*</nowiki>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)
 
<sup>a</sup>May be inconsequential in melanocytic proliferations with Spitzoid morphology; <sup>b</sup>Reported 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 [<nowiki>PMID 41898865</nowiki><ref name=":0" />; open access].  
{| class="wikitable"
{| class="wikitable"
|+
|+
Line 383: Line 388:
|0 (83)
|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.
<nowiki>*</nowiki>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 [<nowiki>PMID 41898865</nowiki><ref name=":0" />; open access].
{| class="wikitable"
{| class="wikitable"
|+
|+
Line 428: Line 436:
|169
|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.'''
<nowiki>*</nowiki>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 [<nowiki>PMID 41898865</nowiki><ref name=":0" />; open access].
{| class="wikitable"
{| class="wikitable"
|+
|+
Line 481: Line 492:
|28
|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 [<nowiki>PMID 41898865</nowiki><ref name=":0" />; open access].''
{| class="wikitable"
|'''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 [<nowiki>PMID 41898865</nowiki><ref name=":0" />; open access].
{| class="wikitable"
|'''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
|}
<nowiki>*</nowiki>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 [<nowiki>PMID 41898865</nowiki><ref name=":0" />; open access].
{| class="wikitable"
|'''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
|}
<nowiki>*</nowiki>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 [<nowiki>PMID 41898865</nowiki><ref name=":0" />; open access].
{| class="wikitable"
|'''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 [<nowiki>PMID 41898865</nowiki><ref name=":0" />; open access].
{| class="wikitable"
|'''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
|}
==Reference==

Latest revision as of 07:56, 26 April 2026

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[1]; 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[1]; 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[1]; 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[1]; 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[1]; 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[1]; 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[1]; 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[1]; 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[1]; 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

Reference

  1. ↑ 1.0 1.1 1.2 1.3 1.4 1.5 1.6 1.7 1.8 Reyes Barron, Cynthia; Geiersbach, Katherine B.; Alomari, Ahmed K.; Deak, Kristen L.; Golem, Shivani; Williams, Eli S.; Aypar, Umut; Zou, Ying S.; Wei, Lei (2026-03-18). "Clinical Utility of Copy Number Abnormality Analysis in the Evaluation of Melanocytic Lesions for Diagnosis and Prognosis: An Evidence-Based Review from the Cancer Genomics Consortium Working Group for Melanocytic Lesions". Genes. 17 (3): 331. doi:10.3390/genes17030331. ISSN 2073-4425. PMC 13026022. PMID 41898865.{{cite journal}}: CS1 maint: unflagged free DOI (link)
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