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.
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
Isolation using the Perkin Elmer™Chemagen™ Chemagen™ Automated Extraction method or Qiagen™ Puregene kit for DNA extraction is recommended.
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
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.