Malignant Melanoma (CDKN2A/p16)
Cutaneous malignant melanoma syndrome (CMM), also known as familial atypical mole-malignant melanoma (FAMMM) syndrome, is characterized by increased risk for this potentially fatal form of skin cancer, often associated with dysplastic or atypical nevi.
PrintCutaneous malignant melanoma syndrome (CMM), also known as familial atypical mole-malignant melanoma (FAMMM) syndrome, is characterized by increased risk for this potentially fatal form of skin cancer, often associated with dysplastic or atypical nevi.
Approximately 10% of cases are a result of germline mutations in the cyclin-dependent kinase inhibitor 2A gene (CDKN2A). CDKN2A encodes two distinct proteins, p16 and p14ARF, translated in alternate reading frames (ARFs); both of these proteins are involved in cell cycle regulation. The majority of reported mutations in the CDKN2A gene affect the p16 protein. Mutations in this gene are inherited in an autosomal dominant manner and contribute to increased cancer risks. Studies have shown mutations in CDKN2A contribute to 10-39% of hereditary form of malignant melanoma. Other studies have also shown an increased risk for pancreatic cancer in families with a CDKN2A mutation.
The Ambry Test: Malignant Melanoma is a gene sequence analysis which detects approximately 94% of described mutations in CDKN2A.
Cutaneous malignant melanoma syndrome (CMM), also known as familial atypical mole-malignant melanoma (FAMMM) syndrome, is characterized by an increased risk for this potentially fatal form of skin cancer, often associated with dysplastic or atypical nevi. Approximately 10% of cases are a result of germline mutations in the cyclin-dependent kinase inhibitor 2A gene (CDKN2A). CDKN2A encodes two distinct proteins, p16 and p14ARF, translated in alternate reading frames (ARFs); both of these proteins are involved in cell cycle regulation. The majority of reported mutations in the CDKN2A gene affect the p16 protein. Mutations in this gene are inherited in an autosomal dominant manner and contribute to increased cancer risks. Studies have shown mutations in CDKN2A contribute to 10-39% of hereditary form of malignant melanoma.1,2,3 Other studies have also shown an increased risk for pancreatic cancer in families with a CDKN2A mutation.
Genetic testing for CDKN2A mutations can identify individuals at hereditary risk for melanoma. Increased surveillance for individuals with a CDKN2A mutation may help reduce morbidity and mortality associated with melanoma. An essential part of patient management is the early diagnosis of melanoma, specifically by identifying lesions in transition from nevi to melanoma. Survival after melanoma is directly related to tumor thickness. As a result, it is important to detect melanomas early by recognizing and performing a biopsy on clinically suspicious lesions.
The Ambry Test: Malignant Melanoma is a full gene sequence analysis performed by PCR-based double-stranded automated sequencing in the sense and antisense directions for exons 1α-3 of the CDKN2A gene, plus at least 20 bases into the 5’ and 3’ ends of all the introns. Specific mutation analysis is also available for individual CDKN2A mutations identified in the family.
Mutations in the CDKN2A gene can be detected in 25-40% of families with two or more cases of melanoma.2,3 The Ambry Test: Malignant Melanoma is capable of detecting approximately 94% of described mutations in CDKN2A.
Blood: Collect 3-5 cc from adult or 2 cc minimum from child into EDTA purple-top tube (first choice) or ACD yellow-top tube (second choice). Store at room temperature or refrigerate. Ship at room temperature.
Saliva: Collect 2 ml into Oragene™ DNA Self-Collection container. Store and ship at room temperature.
DNA: Send 20 µg in TE at 50-100 ng/µl. Store frozen and ship on ice or dry ice.
Prenatal: Prenatal testing is not recommended. Please call an Ambry Genetic Counselor to discuss your case.
| Test Code | Technique | CPT Codes |
|---|---|---|
| 4700 | CDKN2A/p16 Melanoma | 83891x1, 83894x6, 83898x5, 83904x10, 83909x10, 83912x1 |
| Technique | Days |
|---|---|
| CDKN2A/p16 Melanoma | 10-21 |
1 Goldstein AM, Chan M, et al. J Med Genet. 2007; 44:99-106.
2 Goldstein AM & Tucker MA, J Natl Cancer Inst. 1997;89: 676-678.
3 Hayward, NK. Oncogene. 2003; 22:3053-62.
4 De Snoo, FA, et al. Clin Cancer Res. 2008;14: 7151-7157.