DNA icon

Melanoma Predisposition via the CDKN2A Gene

Summary and Pricing

Test Method

Sequencing and CNV Detection via NextGen Sequencing using PG-Select Capture Probes
Test Code Test Copy GenesTest CPT Code Gene CPT Codes Copy CPT Codes Base Price
CDKN2A 81404 81404,81479 $990
Test Code Test Copy Genes Test CPT Code Gene CPT Codes Copy CPT Code Base Price
7397CDKN2A81404 81404,81479 $990 Order Options and Pricing

Pricing Comments

Testing run on PG-select capture probes includes CNV analysis for the gene(s) on the panel but does not permit the optional add on of exome-wide CNV analysis. Any of the NGS platforms allow reflex to other clinically relevant genes, up to whole exome or whole genome sequencing depending upon the base platform selected for the initial test.

An additional 25% charge will be applied to STAT orders. STAT orders are prioritized throughout the testing process.

This test is also offered via a custom panel (click here) on our exome or genome backbone which permits the optional add on of exome-wide CNV or genome-wide SV analysis.

Turnaround Time

3 weeks on average for standard orders or 2 weeks on average for STAT orders.

Please note: Once the testing process begins, an Estimated Report Date (ERD) range will be displayed in the portal. This is the most accurate prediction of when your report will be complete and may differ from the average TAT published on our website. About 85% of our tests will be reported within or before the ERD range. We will notify you of significant delays or holds which will impact the ERD. Learn more about turnaround times here.

Targeted Testing

For ordering sequencing of targeted known variants, go to our Targeted Variants page.


Genetic Counselors


  • Yuan Xue, PhD

Clinical Features and Genetics

Clinical Features

Melanoma is a malignant tumor that originated in melanocytes, a specialized cell type that produces melanin pigments that determine skin, hair and eye color (Lin and Fisher. Nature 445:843–850, 2007). Over the past few decades there has been a rise in the incidence of melanoma due both to improved awareness leading to additional diagnoses and to lifestyle changes that have resulted in an increase in sun exposure (Mehnert and Kluger. Curr Oncol Rep 14:449–457, 2012). Most melanomas occur as sporadic cases with no recognized familial component; however melanoma has been reported to be twice as common in persons with an affected parent, three times as common if a sibling is affected, and nine times as common if both a parent and a sibling are affected (Hemminki et al. J Invest Dermatol 120:217–223, 2003). Familial clustering is likely the result of genetic and environmental factors. Heritable alleles for melanoma susceptibility range from high-risk, high-penetrance alleles that are rare, to low-risk, low-penetrance alleles that are common (Nelson et al. Clinics in Dermatology 27, 46–52, 2009). Mutations in the highly penetrant gene CDKN2A, and less frequently the CDK4 gene, are responsible for the majority of predisposition to melanoma cases. Individuals with genetic predisposition to melanoma have an earlier age of onset. For example, the median age at melanoma diagnosis is significantly lower in carriers of CDKN2A mutations (36 years) than in patients from families with wildtype CDKN2A (45 years) (Goldstein et al. Cancer Res 66:9818–9828, 2006). A family history of melanoma and pancreatic cancer may also suggest inherited mutations in CDKN2A (Goldstein et al. J Natl Cancer Inst 92(12):1006-10, 2000).


Melanoma predisposition is inherited in an autosomal dominant manner. The strongest genetic risk for the development of melanoma results from heritable alterations in the cyclin-dependent kinase inhibitor 2A (CDKN2A) gene, which encodes two separate but related proteins, p16/INK4a and p14/ARF, by using two different promoters. The CDKN2A gene is a tumor suppressor, and its protein products help regulate cell division and apoptosis (Nelson et al., 2009). The p16/INK4a protein is produced from a transcript generated from exons 1α, 2 and 3, whereas p14ARF is produced, using an alternative reading frame, from a transcript comprising exons 1β, 2 and 3 (Lin and Fisher, 2007). The function of the p16/INK4a protein is to inhibit CDK4/6 protein-mediated phosphorylation of the Rb (Retinoblastoma) tumor suppressor protein; dephosphorylated Rb is the active state. Mutated p16/INK4a leads to phosphorylation of Rb, which in turn results in release of the bound transcription factor E2F, which then allows the cell to undergo unregulated cell division leading to the development of melanoma. p14/ARF exerts its regulation of cell division through its indirect interaction with the p53 protein. p14/ARF binds to and inhibits the HDM2 protein. HDM2 functions to ubiquitinate proteins and target them for degradation, Mutations in p14/ARF abrogate binding to HDM2. As a result, HDM2 is released and increases ubiquitination of p53 leading to increased destruction of this tumor suppressor. The main functions of p53 are to sense genetic damage to allow pause for DNA repair and to activate cellular apoptosis. Thus, the decreased levels of p53 associated with mutations in p14/ARF lead to genetic instability and to a higher risk of melanoma in individuals with CDKN2A mutations (Lin and Fisher, 2007). Families with mutated p14/ARF proteins also have an increase in neural system tumors in addition to melanoma (Nelson et al., 2009). CDKN2A causative mutations reported to date include mostly missense mutations, however nonsense, splicing, small insertions and deletions, regulatory, and gross insertions and deletions have also been reported (Human Gene Mutation Database).

Clinical Sensitivity - Sequencing with CNV PG-Select

It has been reported that 25% to 50% of familial melanoma kindreds are affected by a CDKN2A causative mutation (Goldstein et al. J Med Genet 44(2):99-106, 2007). Individuals with multiple primary melanomas have a 1-3% chance of having a CDKN2A causative mutation (Berwick et al. Cancer Epidemiol Biomarkers Prev 15:1520-5, 2006).

Testing Strategy

This test provides full coverage of all coding exons of the CDKN2A gene, plus ~10 bases of flanking noncoding DNA. We define full coverage as >20X NGS reads or Sanger sequencing.

Indications for Test

Candidates for this test are Individuals who have multiple family members with melanoma. Some members of the melanoma families may have other forms of cancer, particularly pancreatic cancer (Goldstein et al., 2000). In such families, it is best to test an affected individual first. Other candidates are patients with multiple primary melanomas. This test is specifically designed for heritable germline mutations and is not appropriate for the detection of somatic mutations in tumor tissue.


Official Gene Symbol OMIM ID
CDKN2A 600160
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT


  • Berwick M. 2006. The Prevalence of CDKN2A Germ-Line Mutations and Relative Risk for Cutaneous Malignant Melanoma: An International Population-Based Study. Cancer Epidemiology Biomarkers & Prevention 15: 15201525. PubMed ID: 16896043
  • Goldstein AM, Chan M, Harland M, Hayward NK, Demenais F, Timothy Bishop D, Azizi E, Bergman W, Bianchi-Scarra G, Bruno W, Calista D, Cannon Albright LA, et al. 2006. Features associated with germline CDKN2A mutations: a GenoMEL study of melanoma-prone families from three continents. Journal of Medical Genetics 44: 99106. PubMed ID: 16905682
  • Goldstein et al. (2000) "Genotype-phenotype relationships in U.S. melanoma-prone families with CDKN2A and CDK4 mutations."J Natl Cancer Inst 92(12):1006-10. PubMed ID: 10861313
  • Goldstein et al. (2006). "High-risk melanoma susceptibility genes and pancreatic cancer, neural system tumors, and uveal melanoma across GenoMEL." Cancer Res 66:98189828. PubMed ID: 17047042
  • Hemminki et al. (2003). "Familial and attributable risks in cutaneous melanoma: effects of proband and age." J Invest Dermatol 120:217223. PubMed ID: 12542525
  • Human Gene Mutation Database (Bio-base).
  • Lin JY, Fisher DE. 2007. Melanocyte biology and skin pigmentation. Nature 445: 843850. PubMed ID: 17314970
  • Mehnert and Kluger. (2012). "Driver mutations in melanoma: lessons learned from bench-to-bedside studies." Curr Oncol Rep14:449457. PubMed ID: 22723080
  • Nelson AA, Tsao H. 2009. Melanoma and genetics. Clinics in Dermatology 27: 4652. PubMed ID: 19095153


Ordering Options

We offer several options when ordering sequencing tests. For more information on these options, see our Ordering Instructions page. To view available options, click on the Order Options button within the test description.

myPrevent - Online Ordering

  • The test can be added to your online orders in the Summary and Pricing section.
  • Once the test has been added log in to myPrevent to fill out an online requisition form.
  • PGnome sequencing panels can be ordered via the myPrevent portal only at this time.

Requisition Form

  • A completed requisition form must accompany all specimens.
  • Billing information along with specimen and shipping instructions are within the requisition form.
  • All testing must be ordered by a qualified healthcare provider.

For Requisition Forms, visit our Forms page

If ordering a Duo or Trio test, the proband and all comparator samples are required to initiate testing. If we do not receive all required samples for the test ordered within 21 days, we will convert the order to the most effective testing strategy with the samples available. Prior authorization and/or billing in place may be impacted by a change in test code.

Specimen Types

Specimen Requirements and Shipping Details

loading Loading... ×


An error has occurred while calculating the price. Please try again or contact us for assistance.

View Ordering Instructions

1) Select Test Method (Platform)

1) Select Test Type

2) Select Additional Test Options

No Additional Test Options are available for this test.

Note: acceptable specimen types are whole blood and DNA from whole blood only.
Total Price: loading
Patient Prompt Pay Price: loading
A patient prompt pay discount is available if payment is made by the patient and received prior to the time of reporting.
Show Patient Prompt Pay Price
Copy Text to Clipboard