Table 1 The classification of melanomas (by 2018 WHO Classification) and associated genomic alterations

I

Low UVR exposure/CSD

Superficial spreading melanoma (SSM)/ skin

BRAF V600 (45–50%) [8]: E (80%)/K (15%) [9] ; NRAS (30%); NF1(15%), triple wild type (WT) (5–10%); KIT (5–10%) [8]

CDKN2A (~ 13–40%: mutation; ~ 45%: loss); TP53(~ 15–18%) [8]

TERT (mutation or gain): 85% [8]

PTEN (8.5–40%) [8]

Low [8]

II

High UVR exposure/CSD

Lentigo malignant melanoma (LMM)/ skin

NRAS (~ 14%) [8]; BRAF (~ 22%) [11]; KIT(~ 10%) [12]

Also mutations in CCND1, MITF, and p53 [13]

III

Desmoplastic melanoma/ skin

BRAF (0–5%); RAS (0–6%); NF1 (52–93%); triple WT (7–48%); KIT (rare) [8]

CDKN2A (20–29%: mutation; 18%: loss); TP53 (40–60%) [8]

TERT (mutation or gain: 85%) [8]

PTEN (rare) [8]

Low [8]

IV

Low to no UVR exposure/CSD

Spitz melanoma/ skin

Spitz associated genetic change include HRAS or MAP2K1 mutations, copy number gains of 11p, and fusions involving ALK, ROS, NTRK1, NTRK2, NTRK3, MET, RET, MAP3K8, and BRAF genes [14]

V

Acral melanoma/ palms, soles or nail beds

BRAF V600 (10–35%); NRAS (8–22%); NF1 (11–23%); triple WT(45–58%); KIT (3–36%) [8]

CDKN2A (0–3%: mutation; 35%: loss); TP53 (6–54%) [8]

TRET (mutation or gain: 9–45%) [8]

PTEN (26–28%) [8]

High [8]

VI

Mucosal melanoma/ mucosa of respiratory, gastrointestinal or urogenital tract

BRAF: 0–21%, RAS: 5–25%, NF1 (0–18%), triple WT: 65–75%, KIT: 7–25% [8]

CDKN2A (rare mutation; 10–38%: loss); TP53: 7–15% [8]

TERT (mutation or gain: 5–13%) [8]

PTEN (4–25%) [8]

High [8]

VII

Melanoma arising in congenital nevus/ skin

BRAF: < 30% mutation, possible fusion [15, 16] NRAS 80–95% [17]

TP53 (rare) [18]

TERT (hypermethylation or gain: case report) [146]

PTEN (proposed role to stop melanoma transformation) [147]

High [17]

VIII

Melanoma arising in blue nevus/ skin

Common GNAQ and GNA11 mutations, occasional PLCB4 or CYSLTR2 mutations, less BRAF or other mutations associated with melanoma, not high TMB [19, 20]

IX

Uveal melanoma/ iris, ciliary body or choroid

Rare BRAF, RAS, and NF1 mutation, triple WT (~ 100%), KIT (11%) [8]

CDKN2A (rare mutation, 12%: loss); TP53 (9%) [8]

TERT (mutation or gain: 5–13%) [8]

PTEN (∼6–11%) [8]

High [8]