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melanoma, cutaneous malignant, susceptibility to, 2 - Clinical Profile, Genes & Research | Kisho | Kisho

Rare Disease

melanoma, cutaneous malignant, susceptibility to, 2

MONDO:0007964

Also known as:Atypical Mole syndromeB-K Mole syndromedysplastic nevus syndrome

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Overview

Clinically atypical nevi (usually exceeding 5 mm in diameter and having variable pigmentation and ill defined borders) with an increased risk for development of non-familial cutaneous malignant melanoma. Biopsies show melanocytic dysplasia. Nevi are clinically and histologically identical to the precursor lesions for melanoma in the B-K mole syndrome. (Stedman, 25th ed)

GeneticsAutosomal dominant

Clinical Trials3 registered · 3 recruiting

Clinical Presentation

Built from Human Phenotype Ontology (HPO) phenotype annotations and GeneReviews clinical descriptions. Features represent findings documented across known cases — not an exhaustive list of possible symptoms.

Features include: Cutaneous melanoma.

GeneReviews

Clinical Guidance

CDKN2A cancer predisposition is characterized by an increased risk of developing multiple cutaneous melanomas, pancreatic cancer, and other tumors including gliomas and astrocytomas. Some affected individuals have a high total nevus count (often 50 nevi) and atypical-appearing nevi, although the number and extent of atypical nevi can vary significantly . Affected individuals from more than 300 families have been identified with a pathogenic variant in CDKN2A [, , , , ]. The following description of the phenotypic features associated with this condition is based on these reports. Table 2. CDKN2A Cancer Predisposition: Frequency of Select Features

Diagnosis

Drawn from GeneReviews diagnostic guidelines, newborn screening panel status (RUSP), and ClinGen gene-disease validity classifications. Reflects current clinical evidence and consensus where available.

GeneReviews

Diagnostic Criteria

Suggestive Findings

CDKN2A cancer predisposition should be suspected in probands with the following clinical findings and family history. Clinical findings

≥3 cutaneous melanomas at any age
Pancreatic cancer and melanoma at any age
≥1 melanoma AND multiple melanocytic nevi (50)

Treatment

Compiled from FDA-approved drug records, orphan drug designations, and FDA Adverse Event Reporting System (FAERS) safety data. GeneReviews management guidance is included where available.

No approved treatments are currently available for melanoma, cutaneous malignant, susceptibility to, 2. The disease remains an area of unmet medical need.

GeneReviews

Management Guidelines

The National Comprehensive Cancer Network has clinical practice guidelines for the care of individuals with CDKN2A cancer predisposition (see NCCN Guidelines, Genetic/Familial High-Risk Assessment: Breast, Ovarian, Pancreatic, and Prostate Version 2.2025 [login required; accessed 1-8-25]). The American Society for Gastrointestinal Endoscopy provides clinical practice guidelines specific to genetic susceptibility for pancreatic cancer . Evaluations Following Initial Diagnosis To establish the extent of disease and needs in an individual diagnosed with CDKN2A cancer predisposition, the evaluations summarized (if not performed as part of the evaluation that led to the diagnosis) are recommended. Table 4. CDKN2A Cancer Predisposition: Recommended Evaluations Following Initial Diagnosis

Prognosis

Based on GeneReviews surveillance recommendations, HPO phenotype frequency and severity annotations, and published prevalence estimates from Orphanet and OMIM.

GeneReviews

Surveillance Guidelines

To monitor existing manifestations, the individual's response to supportive care, and the emergence of new manifestations, the evaluations summarized in are recommended. To date, specific surveillance guidelines for those with a CDKN2A pathogenic variant that affects p14 ARF or p16INK have not been published, although annual full-body and brain MRI can be considered for individuals with pathogenic variants disrupting p14ARF (see NCCN Guidelines, Genetic/Familial High-Risk Assessment: Breast, Ovarian, Pancreatic, and Prostate Version 2.2025 [login required; accessed 1-8-25]). Table 6. CDKN2A Cancer Predisposition: Recommended Surveillance

Research Landscape

Sourced from ClinicalTrials.gov and PubMed. Publication types are classified using NLM-curated article metadata; research type breakdowns reflect the nature of published work for this disease.

3 clinical trials registered, 3 recruiting. Interventions under study include other interventions and drug therapy. Research is primarily sponsored by academic and government institutions.

41 publications have been identified in PubMed for melanoma, cutaneous malignant, susceptibility to, 2. Research spans Epidemiology / Natural History (24%), Review / Meta-Analysis (22%), and Diagnostic / Biomarker (20%).

Research Type	Count	% of Total
Disease patterns and progression	10

Data assembled from 6 of 12 sources · Last updated Sep 18, 2026, 7:16 PM UTC

MONDOHPOClinicalTrials.govFDAPubMedHGNCClinVarClinGenGeneReviewsOrphanetOMIMRUSP

Medical References

External Resources

OMIM

Online Mendelian Inheritance in Man

OMIM:155601

Questions for Your Care Team

→Are any of the 3 active clinical trials a good fit for my situation?
→Are there specialists or centers of excellence for this condition in my area?
→Is there a patient registry I should consider joining?

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Cancer Type	General Population Risk	Risk for Malignancy	Comment
Melanoma	Up to 3%	28%-76%1	Risk may be impacted by geographic location sun exposure.2
Pancreatic	2%	15%-20%3	NA
Nervous system tumors	0.001%5	NA	Elevated6

GeneReviews

Differential Diagnosis

Other cancer/tumor predisposition syndromes associated with melanoma and/or pancreatic cancer are listed in . Table 3. Hereditary Cancer Syndromes of Interest in the Differential Diagnosis of CDKN2A Cancer Predisposition

Gene	Cancer Predisposition Syndrome	MOI	Associated Cancer Predisposition
ATM	ATM-related pancreatic cancer susceptibility2	AD	Pancreatic
BAP1 tumor predisposition syndrome	AD	Cutaneous melanoma	BAP1-inactivated melanocytic tumors; Uveal melanoma; Malignant mesothelioma; Renal cell carcinoma; Basal cell carcinoma BRCA1
BRCA1-associated hereditary breast ovarian cancer	AD	Pancreatic	Breast; Ovarian; Prostate BRCA2
BRCA2-associated hereditary breast ovarian cancer	AD	Cutaneous melanoma; Pancreatic	Breast; Ovarian; Prostate
CDK4	Susceptibility to cutaneous malignant melanoma 3 (OMIM 609048)	AD	Cutaneous melanoma
MITF	Susceptibility to cutaneous malignant melanoma 8 (OMIM 614456)	AD	Cutaneous melanoma
Lynch syndrome	AD	Pancreatic	Colorectal; Endometrium; Ovarian; Gastric; Small bowel; Urinary tract; Biliary tract; Brain; Skin (sebaceous adenomas, sebaceous carcinomas, keratoacanthomas); Prostate
PALB2	PALB2-related pancreatic cancer susceptibility2	AD	Pancreatic
POT1 tumor predisposition	AD	Cutaneous melanoma	Chronic lymphocytic leukemia; Angiosarcoma; Glioma PTEN
PTEN hamartoma tumor syndrome	AD	Cutaneous melanoma	Thyroid; Breast; Kidney; Endometrium; Brain/CNS tumors STK11
Peutz-Jeghers syndrome	AD	Pancreatic	Colorectal; Gastric; Breast; Ovarian
TERT	Susceptibility to cutaneous malignant melanoma 9 (OMIM 615134)	AD	Cutaneous melanoma
Li-Fraumeni syndrome	AD	Cutaneous melanoma; Pancreatic	Adrenocortical carcinoma; Breast; CNS tumors; Osteosarcoma; Soft-tissue sarcoma; Leukemia; Gastrointestinal cancers; Lung AD = autosomal dominant; CNS = central nervous system; MOI = mode of inheritance 1. See linked GeneReview or OMIM entry for additional associated cancer types/tumors. 2.

Source: GeneReviews — "CDKN2A Cancer Predisposition"

System/Concern	Evaluation	Comment
Melanoma	Dermatologic exam for melanoma	Beginning at diagnosis1
Pancreatic cancer	Magnetic resonance cholangiopancreatography or endoscopic ultrasound2	Beginning at age 40 yrs or 10 yrs younger than earliest exocrine pancreatic cancer diagnosis in family, whichever is earlier3,4
Nervous system tumors	Full-body brain MRI	Consider in persons w/CDKN2A pathogenic variants affecting p14ARF isoform in setting of family history of nervous system tumors.3
Genetic counseling	By genetics professionals5	To obtain a pedigree inform affected persons their families re nature, MOI, implications of CDKN2A cancer predisposition to facilitate medical personal decision making MOI = mode of inheritance Published clinical practice guidelines do not provide a starting age.
CDKN2A Cancer Predisposition: Recommended Surveillance System/Concern	Evaluation	Frequency
Melanoma	Dermatologic exam for melanoma	Every 6 mos beginning at diagnosis1; Note: Individuals at risk but whose genetic status is unknown should undergo skin exams at their well child/ health maintenance visits. Self-skin exam
Pancreatic cancer	Magnetic resonance cholangiopancreatography or endoscopic ultrasound2	Annually (alternating); Starting at age 40 yrs or 10 yrs younger than earliest exocrine pancreatic cancer diagnosis in family, whichever is earlier
Nervous system tumors	Full-body brain MRI	Consider annually in those w/CDKN2A pathogenic variants affecting p14ARF isoform in setting of family history of nervous system tumors.3 Published clinical practice guidelines do not provide a starting age. Melanoma has been reported as young as age nine years .

System/Concern	Evaluation	Frequency
Melanoma	Dermatologic exam for melanoma	Every 6 mos beginning at diagnosis1; Note: Individuals at risk but whose genetic status is unknown should undergo skin exams at their well child/ health maintenance visits. Self-skin exam
Pancreatic cancer	Magnetic resonance cholangiopancreatography or endoscopic ultrasound2	Annually (alternating); Starting at age 40 yrs or 10 yrs younger than earliest exocrine pancreatic cancer diagnosis in family, whichever is earlier
Nervous system tumors	Full-body brain MRI	Consider annually in those w/CDKN2A pathogenic variants affecting p14ARF isoform in setting of family history of nervous system tumors.3 Published clinical practice guidelines do not provide a starting age. Melanoma has been reported as young as age nine years .

Kisho

melanoma, cutaneous malignant, susceptibility to, 2

Overview

Clinical Presentation

Clinical Guidance

Diagnosis

Diagnostic Criteria

Suggestive Findings

Treatment

Management Guidelines

Prognosis

Surveillance Guidelines

Research Landscape

Medical References

External Resources

OMIM

Questions for Your Care Team

Questions for Your Care Team

Explore clinical features

Establishing the Diagnosis

Differential Diagnosis

Clinical Guidance

Therapies Under Investigation

Clinical Trials

Recent Publications

melanoma, cutaneous malignant, susceptibility to, 2

Overview

Clinical Presentation

Clinical Guidance

Diagnosis

Diagnostic Criteria

Suggestive Findings

Treatment

Management Guidelines

Prognosis

Surveillance Guidelines

Research Landscape

Medical References

External Resources

OMIM

Related Diseases

Questions for Your Care Team

Questions for Your Care Team

Explore clinical features

Establishing the Diagnosis

Differential Diagnosis

Clinical Guidance

Therapies Under Investigation

Clinical Trials

Recent Publications