Table 3.

Main genomic alterations in malignant melanoma.

Genes	Incidence	Pathway	Actions	MMs Type
BRAF (BRAFV600E BRAFV600 BRAFV600K BRAFK601E)	45%	MAPK/ERK signalling	melanocytes cellular cycle, differentiation, and apoptosis	sun exposed cutaneous melanoma
	<10%			mucosal melanoma
RAS	15–30%	activation of downstream signalling	melanocytes proliferation, differentiation, and survival	sun-exposed cutaneous melanoma
NRAS	15%	MAPK/PI3K signalling	melanocytes proliferation, differentiation, and survival	sun-exposed cutaneous melanoma
c-KIT (CD117)	<3%	activation of MAPK and PI3K/AKT pathways	melanocytes proliferation and survival regulation	sun-exposed cutaneous melanoma
	40%			mucosal melanoma
ATRX	9.11%	regulation of chromosomal segregation in mitosis	melanoma progression	mucosal and cutaneous melanoma
ARID2	13.32%	gene transcription mechanism promoter	tumour immunity regulation	mucosal melanoma
SETD2	9.48%	methylation of histone H3 lysine 36	aberrant differentiation or proliferation of melanocytes	mucosal melanoma
GNAQ/GNA11	80–90%	MAPK signalling	melanocytes proliferation	uveal melanoma rare in cutaneous melanoma
BAP1	6.13%	ubiquitin-proteasome system and DNA damage response	melanocytes growth and proliferation regulation	spitzoid tumour uveal melanoma
SF3B1	33%	RNA splicing	tumourigenesis	mucosal melanoma
NF1	10–15%	downregulation of Rat Sarcoma (RAS) proteins and MAPK/PI3K signalling	melanocytes growing and survival	sun-exposed cutaneous melanomas
RAC1	9.2%	activated MAPK signalling	increased melanocytes proliferation and altered cell migration	sun-exposed cutaneous melanoma
TERT	14%	chromosomal telomere length maintenance	melanocytes survival support	cutaneous melanoma
KRAS	2.9%	GTPase activity	melanocytes proliferation and survival	cutaneous melanomas
ERBB2/4	3.29%	tyrosine kinases signalling	melanocytes proliferation and survival	cutaneous melanomas
CDKN2A	25–35%	RB pathway	apoptosis and melanocytes survival	cutaneous melanomas
TP53	15%	tumour suppressor and transcriptional activator/repressor of several downstream genes	increased melanocytes proliferation and reduced apoptosis	sun-exposed cutaneous melanomas
PTEN	14%	PI3K signalling	increased mitogen signalling and cell survival	cutaneous melanoma
MAP2K1/2	10%	MAPK signalling	melanocytes proliferation	cutaneous melanoma

ARID2—AT rich interactive domain 2; ATRX—alpha thalassemia/mental retardation syndrome X-linked; BAP1—BRCA1 associated protein 1; BRAF—B-Raf proto-oncogene, serine/threonine kinase; CD117—cluster of differentiation 117; CDKN2A—cyclin-dependent kinase inhibitor 2A; c-kit—mast/stem cell growth factor receptor kit; DNA—deoxyribonucleic acid; ERBB2/4—Erb-b2 receptor tyrosine kinase 2/4; GNAQ—G protein subunit α Q; GNA11—G-protein subunit α11; GTPase—nucleotide guanosine triphosphatase; KRAS—Kirsten rat sarcoma viral oncogene homolog; MAP2K1/2—mitogen-activated protein kinase kinase 1 and 2; MAPK/ERK—mitogen-activated protein kinase/extracellular signal-regulated kinase; MM—malignant melanoma; NF1—neurofibromin 1; NRAS—neuroblastoma RAS viral oncogene homolog; PI3K—phosphoinositide 3-kinases; PTEN—phosphatase and tensin homolog; RAC1—Ras-related C3 botulinum toxin substrate 1; RAS—rat sarcoma virus; RB—retinoblastoma tumour suppressor; SETD2—SET domain containing 2, histone lysine methyltransferase; SF3B1—splicing factor 3b subunit 1; TERT—telomerase reverse transcriptase (TERT) promoter region; TP53—tumour protein 53.