Compendium of Cancer Genome Aberrations

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 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"
|+
|'''Event Type'''
|'''Region'''
|'''Rate of Gain or Loss (%)'''
|'''Possible Genes Affected'''
|-
| rowspan="45" |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'' ***
|-
| rowspan="32" |Loss
|1p
|23
|
|-
|1p36
|32
|''PRDM16'' ***, ''ARID1A'' **
|-
|3p21<sup>a</sup>
|15
|''BAP1'' **
|-
|3q
|14
|
|-
|4q
|10
|
|-
|5q
|22
|
|-
|6q
|14
|
|-
|6q23
|29
|''MYB'' ***
|-
|6q25<sup>b</sup>
|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'' ***
|}
<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"
|+
|'''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)
|}
<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"
|+
|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
|}
<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"
|+
!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 [<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==
Retrieved from "https://content.ccga.io/index.php/Melanocytic_Lesions"