Melanoma-Pancreatic Cancer: CDKN2A Gene Deletion/Duplication

Condition Description

Members offamilies with melanoma-pancreatic cancer syndrome (also known as familialatypical multiple-mole melanoma (FAMMM) syndrome) inherit a predisposition todevelop multiple atypical cutaneous nevi (> 50), although not all patientswith melanoma in these families display this phenotype. These families alsoappear to be at increased risk of other malignancies, particularlyadenocarcinoma of the pancreas. A melanoma family apparently predisposed to pancreaticcancer was reported first in 1968, and a number of additional families havebeen identified subsequently. Several studies of melanoma-pancreatic cancersyndrome families have found an excess of nonmelanoma malignancies comparedwith the expected frequency of these malignancies in the general population.The risk of developing malignant disease in these families appears to beincreased 10-fold to 40-fold, and the cumulative risk of pancreatic cancer, thesecond most common cancer in the syndrome, has been estimated at 17% by age 75years. In addition, these families may be at increased risk of developing othercarcinomas, including breast tumors, lung tumors, sarcoma, and digestive tracttumors.

The mostcommon known mutation in these melanoma-prone families involves the CDKN2Agene on chromosome 9p21. CDKN2A encodes p16, a low-molecular-weight protein that inhibits the cyclinD1-cyclin dependent kinase complex (CDK4).If it is not inhibited, the CDK4complex, in turn, phosphorylates the retinoblastoma protein, allowing a cell toprogress through the G1 phase of the cell cycle. Thus, p16 acts as a tumor suppressor protein, and mutations in CDKN2Acan result in unregulated cell growth and neoplastic progression. Germ line CDKN2Amutations have been detected in up to 25% of melanoma-prone families worldwide.


Rulyak, S, Brentnall, T, Lynch, H, Austin, M.Characterization of the neoplastic phenotype in the familial atypicalmultiple-mole melanoma-pancreatic carcinoma syndrome. 2003. Cancer 98(4):798-804.

Genes (1)

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This test is indicated for:

  • Confirmation of a clinical diagnosis of melanoma-pancreatic cancer syndrome in individuals who have tested negative for sequence analysis
  • Individuals at-risk for melanoma-pancreatic cancer syndrome due to family history who have tested negative for sequence analysis


DNA isolated from peripheral blood is hybridized to a CGH array to detect deletions and duplications. The targeted CGH array has overlapping probes which cover the entire genomic region.


Detection is limited to duplications and deletions. The CGH array will not detect point or intronic mutations. Results of molecular analysis must be interpreted in the context of the patient's clinical and/or biochemical phenotype.

Specimen Requirements

Listed below are EGL's preferred sample criteria. For any questions, please call 470.378.2200 and ask to speak with a laboratory genetic counselor (
Submit only 1 of the following specimen types
DNA, Isolated

Isolation using the Perkin Elmer™Chemagen™ Chemagen™ Automated Extraction method or Qiagen™ Puregene kit for DNA extraction is recommended.
Collection and Shipping
Refrigerate until time of shipment in 100 ng/µL in TE buffer. Ship sample at room temperature with overnight delivery.
Whole Blood (EDTA)

EDTA (Purple Top)
Infants and Young Children (<2 years of age): 2-3 ml
Children > 2 years of age to 10 years old: 3-5 ml
Older Children & Adults: 5-10 ml
Autopsy: 2-3 ml unclotted cord or cardiac blood
Collection and Shipping
Ship sample at room temperature for receipt at EGL within 72 hours of collection. Do not freeze.

Special Instructions

Submit copies of diagnostic biochemical test results with the sample, if appropriate. Contact the laboratory if further information is needed.

Sequence analysis is required before deletion/duplication analysis by targeted CGH array. If sequencing is performed outside of EGL Genetics, please submit a copy of the sequencing report with the test requisition.

  • Sequencing analysis of the CDKN2A gene is available (VN) and is required before deletion/duplication analysis.
  • Prenataltesting is available to individuals who are confirmed carriers ofmutations. Please contact the laboratory genetic counselor to discussappropriate testing prior to collecting a prenatal specimen.

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