Acral lentiginous melanoma

Summary

Acral lentiginous melanoma (MONDO:0003865) is a cancer with 2 cohort genes (2 CIViC-evidence somatic drivers) and 28 clinical trials. Molecularly, EMSY Amplification confers sensitivity to Talazoparib in Acral Lentiginous Melanoma (CIViC Level C). Top therapeutic interventions include nilotinib, binimetinib, and encorafenib.

At a glance

• Classification: Cancer
• Cohort genes: 2
• Clinical trials: 28
• Precision-medicine evidence (CIViC): 1 subtype–drug association

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	acral lentiginous melanoma
Mondo ID	MONDO:0003865
DOID	DOID:6367
NCIT	C4022
SNOMED CT	254732008
UMLS	C0346037
MedGen	87530
Is cancer (heuristic)	yes

Also known as: acral lentiginous malignant melanoma · acral lentiginous malignant melanoma of skin · acral lentiginous melanoma · acral lentiginous melanoma (disease) · acral lentiginous melanoma, malignant · acral lentiginous melanoma, malignant (morphologic abnormality) · acral melanoma · ALM · palmar/plantar melanoma · subungual melanoma

Data availability: 1 HPO phenotype · 28 cell lines.

Disease family

Classification path: disease › human disease › disease by body system or component › integumentary system disorder › integumentary system cancer › skin cancer › cutaneous melanoma › acral lentiginous melanoma

Related subtypes (9): eyelid melanoma, balloon cell malignant melanoma, nodular malignant melanoma, amelanotic skin melanoma, superficial spreading melanoma, lentigo maligna melanoma, desmoplastic melanoma, spitzoid melanoma, melanoma in congenital melanocytic nevus

Genetics & variants

GWAS landscape

No GWAS associations recorded — common-variant (GWAS) studies don’t cover this disease (typical for Mendelian / rare diseases). See the curated gene cohort and Mendelian overlap below.

Variant details and genetic-evidence tiers

No tiered GWAS variants or ClinVar records for this disease.

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 27 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Somatic driver evidence (intOGen + CIViC, cohort fanout)

Gene	intOGen role	Cancer types	CIViC
TERT	Act	PRCC	CIViC #79
KIT	Act	AML,GIST,MEL,MGCT	CIViC #29

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
TERT	Orphanet:146	Differentiated thyroid carcinoma
TERT	Orphanet:1501	Adrenocortical carcinoma
TERT	Orphanet:1775	Dyskeratosis congenita
TERT	Orphanet:2032	Idiopathic pulmonary fibrosis
TERT	Orphanet:2495	Meningioma
TERT	Orphanet:3322	Hoyeraal-Hreidarsson syndrome
TERT	Orphanet:457246	Clear cell sarcoma of kidney
TERT	Orphanet:618	Familial melanoma
TERT	Orphanet:88	Idiopathic aplastic anemia
KIT	Orphanet:102724	Acute myeloid leukemia with t(8;21)(q22;q22) translocation
KIT	Orphanet:158766	Typical urticaria pigmentosa
KIT	Orphanet:158769	Plaque-form urticaria pigmentosa
KIT	Orphanet:158772	Nodular urticaria pigmentosa
KIT	Orphanet:158775	Smoldering systemic mastocytosis
KIT	Orphanet:158778	Isolated bone marrow mastocytosis
KIT	Orphanet:280785	Bullous diffuse cutaneous mastocytosis
KIT	Orphanet:280794	Pseudoxanthomatous diffuse cutaneous mastocytosis
KIT	Orphanet:2884	Piebaldism
KIT	Orphanet:44890	Gastrointestinal stromal tumor
KIT	Orphanet:566393	Acute mast cell leukemia
KIT	Orphanet:566396	Chronic mast cell leukemia
KIT	Orphanet:79455	Cutaneous mastocytoma
KIT	Orphanet:842	Testicular seminomatous germ cell tumor
KIT	Orphanet:90389	Telangiectasia macularis eruptiva perstans
KIT	Orphanet:98829	Acute myeloid leukemia with abnormal bone marrow eosinophils inv(16)(p13q22) or t(16;16)(p13;q22)
KIT	Orphanet:98834	Acute myeloblastic leukemia with maturation
KIT	Orphanet:98849	Systemic mastocytosis with associated hematologic neoplasm

Cohort genes → proteins

2 cohort genes, 2 distinct canonical proteins.

Evidence partition

Subset	Genes
civic_only	2

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
TERT	HGNC:11730	ENSG00000164362	O14746	Telomerase reverse transcriptase	civic_evidence
KIT	HGNC:6342	ENSG00000157404	P10721	Mast/stem cell growth factor receptor Kit	civic_evidence

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
TERT	Telomerase reverse transcriptase	Telomerase is a ribonucleoprotein enzyme essential for the replication of chromosome termini in most eukaryotes.
KIT	Mast/stem cell growth factor receptor Kit	Tyrosine-protein kinase that acts as a cell-surface receptor for the cytokine KITLG/SCF and plays an essential role in the regulation of cell survival and proliferation, hematopoiesis, stem cell maintenance, gametogenesis, mast cell develo…

Protein-family classification

Druggable: 1 · Difficult: 0 · Unknown: 1 · Druggable fraction: 0.5

Family distribution

Cohort families vs a genome-wide background (hypergeometric, BH-FDR; fold = observed/expected). Counts kept; sorted by enrichment, so the catch-all Other/Unknown bucket no longer leads.

Family	Genes	Fold	FDR
Kinase	1	13.9×	0.142
Other/Unknown	1	0.9×	0.805

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
TERT	Other/Unknown	no		RT_dom, Telomerase_RT, Telomerase_RBD
KIT	Kinase	yes	2.7.10.1	Prot_kinase_dom, Ser-Thr/Tyr_kinase_cat_dom, Tyr_kinase_rcpt_3_CS

Expression context

Cohort genes with no expression data: 0.

1 cohort gene are a single-cell marker in ≥1 SCXA experiment.

Breadth distribution (Bgee present_calls)

Bucket	Genes
narrow (1-5 tissues)	0
moderate (6-20)	0
broad (>20)	2
unknown	0

Top tissues across cohort

Tissue	Cohort genes
olfactory bulb	1
stromal cell of endometrium	1
type B pancreatic cell	1
lateral nuclear group of thalamus	1
oocyte	1
secondary oocyte	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
TERT	105	broad	yes	stromal cell of endometrium, type B pancreatic cell, olfactory bulb
KIT	263	broad	marker	lateral nuclear group of thalamus, secondary oocyte, oocyte

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
KIT	6,087
TERT	5,717

Structural data

PDB: 2 · AlphaFold-only: 0 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
KIT	P10721	52
TERT	O14746	23

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 49. Enrichment computed across 2 evidence-associated genes (2 with Reactome annotation).

Pathways by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 2 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Dasatinib-resistant KIT mutants	1	5710.0×	7e-04	KIT
Imatinib-resistant KIT mutants	1	5710.0×	7e-04	KIT
KIT mutants bind TKIs	1	5710.0×	7e-04	KIT
Masitinib-resistant KIT mutants	1	5710.0×	7e-04	KIT
Nilotinib-resistant KIT mutants	1	5710.0×	7e-04	KIT
Regorafenib-resistant KIT mutants	1	5710.0×	7e-04	KIT
Signaling by kinase domain mutants of KIT	1	5710.0×	7e-04	KIT
Sunitinib-resistant KIT mutants	1	5710.0×	7e-04	KIT
Signaling by juxtamembrane domain KIT mutants	1	5710.0×	7e-04	KIT
Sorafenib-resistant KIT mutants	1	5710.0×	7e-04	KIT
Drug resistance of KIT mutants	1	5710.0×	7e-04	KIT
Signaling by extracellular domain mutants of KIT	1	5710.0×	7e-04	KIT
MITF-M-regulated melanocyte development	2	114.2×	7e-04	TERT, KIT
Regulation of MITF-M-dependent genes involved in DNA replication, damage repair and senescence	1	815.7×	0.004	TERT
Signaling by KIT in disease	1	571.0×	0.006	KIT
TFAP2 (AP-2) family regulates transcription of growth factors and their receptors	1	380.7×	0.008	KIT
Transcriptional regulation by the AP-2 (TFAP2) family of transcription factors	1	317.2×	0.008	KIT
Developmental Lineage of Mammary Gland Alveolar Cells	1	317.2×	0.008	KIT
Regulation of KIT signaling	1	300.5×	0.008	KIT
Extension of Telomeres	1	300.5×	0.008	TERT
Signaling by phosphorylated juxtamembrane, extracellular and kinase domain KIT mutants	1	259.6×	0.009	KIT
Telomere Extension By Telomerase	1	228.4×	0.009	TERT
Developmental Lineage of Mammary Gland Luminal Epithelial Cells	1	228.4×	0.009	KIT
Developmental Biology	2	14.5×	0.010	TERT, KIT
Telomere Maintenance	1	184.2×	0.010	TERT
PI3K/AKT Signaling in Cancer	1	184.2×	0.010	KIT
Negative regulation of the PI3K/AKT network	1	139.3×	0.013	KIT
Signaling by SCF-KIT	1	124.1×	0.014	KIT
Chromosome Maintenance	1	105.7×	0.016	TERT
Signal Transduction	2	10.2×	0.016	TERT, KIT

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 2 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
response to cadmium ion	2	732.7×	2e-04	TERT, KIT
RNA-templated transcription	1	8426.0×	0.001	TERT
DNA strand elongation	1	8426.0×	0.001	TERT
melanocyte adhesion	1	8426.0×	0.001	KIT
positive regulation of pyloric antrum smooth muscle contraction	1	8426.0×	0.001	KIT
siRNA transcription	1	8426.0×	0.001	TERT
positive regulation of transdifferentiation	1	8426.0×	0.001	TERT
positive regulation of colon smooth muscle contraction	1	8426.0×	0.001	KIT
RNA-templated DNA biosynthetic process	1	4213.0×	0.002	TERT
positive regulation of hair cycle	1	4213.0×	0.002	TERT
positive regulation of vascular associated smooth muscle cell differentiation	1	4213.0×	0.002	KIT
Fc receptor signaling pathway	1	2808.7×	0.002	KIT
Kit signaling pathway	1	2808.7×	0.002	KIT
melanocyte migration	1	2808.7×	0.002	KIT
obsolete regulation of bile acid metabolic process	1	2808.7×	0.002	KIT
positive regulation of small intestine smooth muscle contraction	1	2808.7×	0.002	KIT
mast cell chemotaxis	1	2106.5×	0.003	KIT
hematopoietic stem cell migration	1	2106.5×	0.003	KIT
mast cell differentiation	1	2106.5×	0.003	KIT
positive regulation of dendritic cell cytokine production	1	1685.2×	0.003	KIT
positive regulation of mast cell cytokine production	1	1685.2×	0.003	KIT
mast cell proliferation	1	1685.2×	0.003	KIT
positive regulation of mast cell proliferation	1	1685.2×	0.003	KIT
lymphoid progenitor cell differentiation	1	1404.3×	0.003	KIT
erythropoietin-mediated signaling pathway	1	1404.3×	0.003	KIT
positive regulation of protein localization to nucleolus	1	1404.3×	0.003	TERT
myeloid progenitor cell differentiation	1	1203.7×	0.003	KIT
immature B cell differentiation	1	1203.7×	0.003	KIT
glycosphingolipid metabolic process	1	1203.7×	0.003	KIT
tongue development	1	1053.2×	0.003	KIT

Therapeutics

Drug target analysis

Approved (phase 4): 2 · Phase ≥3: 2 · Phased (≥1): 2 · Undrugged: 0

Druggability breadth: 2 of 2 evidence-associated genes (100%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Genes with an approved drug

The molecule shown is one approved compound that hits the gene — not necessarily a drug of choice or one indicated for this disease.

Symbol	Example approved molecule
TERT	BERBERINE
KIT	PONATINIB

Top cohort targets by molecule count

Symbol	Molecules	Max phase
KIT	99	4
TERT	10	4

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
BERBERINE	4	TERT
DOXORUBICIN	4	TERT
PONATINIB	4	KIT
FEDRATINIB	4	KIT
TIVOZANIB	4	KIT
LENVATINIB	4	KIT
AXITINIB	4	KIT
SORAFENIB	4	KIT
DASATINIB ANHYDROUS	4	KIT
NICLOSAMIDE	4	KIT
IMATINIB MESYLATE	4	KIT
RUXOLITINIB	4	KIT
INFIGRATINIB PHOSPHATE	4	KIT
INFIGRATINIB	4	KIT
REGORAFENIB	4	KIT
ENTRECTINIB	4	KIT
CABOZANTINIB	4	KIT
CERITINIB	4	KIT
VANDETANIB	4	KIT
NILOTINIB	4	KIT
BOSUTINIB	4	KIT
BRIGATINIB	4	KIT
PEXIDARTINIB	4	KIT
AVAPRITINIB	4	KIT
RIPRETINIB	4	KIT
PAZOPANIB	4	KIT
NINTEDANIB	4	KIT
SUNITINIB	4	KIT
DASATINIB	4	KIT
ERLOTINIB	4	KIT

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 1.

Cohort genes with ChEMBL bioactivity (full, sorted by assay count)

Symbol	Assays	Type breakdown
KIT	2,305	Binding:2242, ADMET:32, Functional:22, Toxicity:9
TERT	391	Binding:389, Functional:2

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
KIT	2.7.10.1	receptor protein-tyrosine kinase

Cohort genes with high screening signal

≥100 ChEMBL assays — a studied-ness signal; see Therapeutics for approved-drug status.

Symbol	ChEMBL assays
TERT	391
KIT	2,305

Pharmacogenomics

Cohort genes with a PharmGKB record: 2; with CPIC/DPWG dosing guidelines: 0.

No cohort gene has a CPIC/DPWG genotype-guided dosing guideline (PharmGKB).

Drug repurposing candidates

28 approved/phased drugs hit cohort targets but don’t yet appear in disease-level clinical trials. Target-inhibition rationale is strongest for cancer driver genes; a bioactivity hit is a screening signal, not a treatment claim.

Compound	Max phase	Cohort target (bioactivity)
BERBERINE	4	TERT
DOXORUBICIN	4	TERT
PONATINIB	4	KIT
FEDRATINIB	4	KIT
TIVOZANIB	4	KIT
LENVATINIB	4	KIT
AXITINIB	4	KIT
SORAFENIB	4	KIT
DASATINIB ANHYDROUS	4	KIT
NICLOSAMIDE	4	KIT
IMATINIB MESYLATE	4	KIT
RUXOLITINIB	4	KIT
INFIGRATINIB PHOSPHATE	4	KIT
INFIGRATINIB	4	KIT
REGORAFENIB	4	KIT
ENTRECTINIB	4	KIT
CABOZANTINIB	4	KIT
CERITINIB	4	KIT
VANDETANIB	4	KIT
BOSUTINIB	4	KIT
BRIGATINIB	4	KIT
PEXIDARTINIB	4	KIT
AVAPRITINIB	4	KIT
RIPRETINIB	4	KIT
PAZOPANIB	4	KIT
NINTEDANIB	4	KIT
DASATINIB	4	KIT
ERLOTINIB	4	KIT

Druggability pyramid

Cohort genes binned by druggability tier (high → low):

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	2	TERT, KIT
B	Phased (≥1) drug, not yet approved	0
C	Druggable family + PDB, no drug	0
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	0

Undrugged target profiles

0 cohort genes are undrugged. Ranked by ‘starting-point quality’ (assay depth + drugged-partner adjacency).

Clinical trials & evidence

Clinical trials

Clinical trials: 28.

Phase distribution (across all retrieved trials)

Phase	Trials
PHASE2	19
PHASE1	6
PHASE3	1
PHASE1/PHASE2	1
Not specified	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT05789043	PHASE3	RECRUITING	Camrelizumab in Combination With Apatinib and Temozolomide as First-line Treatment in Advanced Acral Melanoma
NCT00937937	PHASE2	ACTIVE_NOT_RECRUITING	Dinaciclib in Treating Patients With Stage IV Melanoma
NCT03698019	PHASE2	ACTIVE_NOT_RECRUITING	A Study to Compare the Administration of Pembrolizumab After Surgery Versus Administration Both Before and After Surgery for High-Risk Melanoma
NCT04331093	PHASE2	RECRUITING	Neoadjuvant SHR-1210 Plus Apatinib for Resectable Stage III-IV Acral Melanoma
NCT04511013	PHASE2	RECRUITING	A Study to Compare the Administration of Encorafenib + Binimetinib + Nivolumab Versus Ipilimumab + Nivolumab in BRAF-V600 Mutant Melanoma With Brain Metastases
NCT05086692	PHASE1/PHASE2	RECRUITING	A Beta-only IL-2 ImmunoTherapY Study
NCT05512481	PHASE2	RECRUITING	Camrelizumab Plus Apatinib and Temozolomide as Neoadjuvant in High Risk Acral Melanoma
NCT06965231	PHASE2	RECRUITING	Perioperative Toripalimab and Endostatin for Stage II Melanoma: A Phase II Trial
NCT07155317	PHASE2	RECRUITING	Time-of-Day Specified Immunotherapy for Advanced Melanoma, The TIME Trial
NCT07347444	PHASE2	NOT_YET_RECRUITING	Iparomlimab and Tuvoraleimab Injection in Combination With Bevacizumab, Albumin-bound Paclitaxel, and Carboplatin as First- or Second-line Treatment for Patients With Advanced Acral and Mucosal Melanoma
NCT07576725	PHASE2	NOT_YET_RECRUITING	Low Dose, Reduced Frequency Nivolumab for the Treatment of Unresectable or Metastatic Cancer, AFFORD IO Trial
NCT00243061	PHASE2	COMPLETED	AZD2171 in Treating Patients With Recurrent or Stage IV Melanoma
NCT00470470	PHASE2	COMPLETED	Imatinib Mesylate in Treating Patients With Stage III or Stage IV Melanoma That Cannot Be Removed by Surgery
NCT00577382	PHASE2	COMPLETED	SU011248 in Patients With Metastatic Mucosal or Acral/Lentiginous Melanoma
NCT00788775	PHASE2	COMPLETED	Nilotinib in TKI Resistant or Intolerant Patients With Metastatic Mucosal, Acral, or Chronically Sun Damaged Melanoma
NCT01120275	PHASE2	TERMINATED	Gamma-Secretase/Notch Signalling Pathway Inhibitor RO4929097 in Treating Patients With Stage IV Melanoma
NCT01395121	PHASE2	COMPLETED	A Trial Looking at Nilotinib to Treat Acral and Mucosal Melanoma Skin Cancer That Has Spread
NCT02519322	PHASE2	COMPLETED	Neoadjuvant and Adjuvant Checkpoint Blockade
NCT02875132	PHASE2	COMPLETED	Pembrolizumab in Advanced/Metastatic Acral Lentiginous Melanoma
NCT02978443	PHASE2	TERMINATED	A Biomarker Study in Advanced Mucosal or Acral Lentiginous Melanoma Receiving Nivolumab in Combination With Ipilimumab
NCT05436990	PHASE2	TERMINATED	Antitumor Activity of Vactosertib in Combination With Pembrolizumab in Acral and Mucosal Melanoma Patients Progressed From Prior Immune Check Point Inhibitor
NCT03025256	PHASE1	RECRUITING	Intravenous and Intrathecal Nivolumab in Treating Patients With Leptomeningeal Disease
NCT04119024	PHASE1	RECRUITING	Gene Modified Immune Cells After Conditioning Regimen for the Treatment of Stage IIIC or IV Melanoma or Metastatic Solid Tumors
NCT05098210	PHASE1	RECRUITING	Personalized Neo-Antigen Peptide Vaccine for the Treatment of Stage IIIC-IV Melanoma, Hormone Receptor Positive HER2 Negative Metastatic Refractory Breast Cancer or Stage III-IV Non-Small Cell Lung Cancer
NCT04244552	PHASE1	TERMINATED	A Phase 1b Trial of ATRC-101 in Adults With Advanced Solid Malignancies
NCT04653038	PHASE1	TERMINATED	A Study to Evaluate the Safety and Efficacy of MGD013 in Patients With Melanoma
NCT05628883	PHASE1	COMPLETED	Proof of Concept of TBio-4101, Lymphodepleting Chemo, IL-2 for Relapsed/Refractory Melanoma
NCT06661577	Not specified	NOT_YET_RECRUITING	An Observational Study Using The LumAssure Device In Participants Undergoing Assessment Of Skin Conditions.

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
NILOTINIB	4	2
BINIMETINIB	4	1
ENCORAFENIB	4	1
RELATLIMAB	4	1
SUNITINIB	4	1
RIVOCERANIB	3	3
CAMRELIZUMAB	3	1
CEDIRANIB MALEATE	3	1
DINACICLIB	3	1
ALEXTATUG	2	1
HILTONOL	2	1
TEBOTELIMAB	2	1
VACTOSERTIB	2	1
CHEMBL275117	0	1
CHEMBL4517714	0	1
CHEMBL5405436	0	1
CHEMBL2006674	0	1
CHEMBL5171657	0	1
CHEMBL5408374	0	1
CHEMBL5267324	0	1

Precision-medicine subtype map (CIViC)

Drug × molecular subtype: 1 predictive associations from 1 curated evidence items; also 1 prognostic, 1 diagnostic.

Molecular subtype	Therapy	Effect	Level	CIViC
EMSY Amplification	Talazoparib	Sensitivity/Response	CIViC C	EID12148