Multiple primary melanoma revisited.
BACKGROUND
Incidence of cutaneous melanoma continues to increase in the Caucasian population worldwide. Approximately 5% of melanoma patients develop additional primary melanoma. This rate is significantly higher than the estimated lifetime risk of an individual for developing the disease (1.4%). These features suggest that a genetic predisposition may underlie multiple primary melanomas (MPMs). Prior studies had identified CDKN2A mutations in a few MPM individuals. The objectives of this study were to determine the frequency of family history of melanoma in MPM cases, to characterize other clinical features including history of other cancer, and to determine the association with functional CDKN2A mutations.


METHODS
This study used a case series design. All living patients who had been seen in the Pigmented Lesion Clinic at the University of Pennsylvania and who had more than one primary invasive malignant melanoma or an invasive primary followed by an in situ melanoma were eligible for participation.


RESULTS
Individuals with MPM frequently had a family history of melanoma, dysplastic nevi (DN), and/or another cancer including basal cell carcinoma (BCC), and squamous cell carcinoma breast cancer, and a personal history of DN, and basal cell carcinoma. Germline mutations in CDKN2A gene were identified in 8 of 96 MPM cases (8.3%, 95% confidence interval, 6.7-9.9%).


CONCLUSIONS
These data indicate that the presence of MPM is associated with a modest incidence of a family history of melanoma, DN, or BCC and a small association with CDKN2A mutations. Therefore, in addition to the MPM index case, other family members can benefit from screening and regular surveillance for melanoma, DN, and BCC.
Blackwood
M Anne
MA
Department of Medicine, Hematology-Oncology Division, University of Pennsylvania, Philadelphia, Pennsylvania 19104-6145, USA.
Holmes
Robin
R
Synnestvedt
Marie
M
Young
Megan
M
George
Cicily
C
Yang
Hannah
H
Elder
David E
DE
Schuchter
Lynn M
LM
Guerry
DuPont
D
Ganguly
Arupa
A
D000293:Adolescent; D000328:Adult; D017668:Age of Onset; D000368:Aged; D000369:Aged, 80 and over; D001943:Breast Neoplasms / Q000235:genetics; D002280:Basal Cell Carcinoma / Q000235:genetics; D002294:Carcinoma, Squamous Cell / Q000235:genetics; D004252:DNA Mutational Analysis / Q000379:methods; D017931:DNA Primers / Q000737:chemistry; D004273:DNA, Neoplasm / Q000378:metabolism; D004416:Dysplastic Nevus Syndrome / Q000235:genetics* / Q000473:pathology; D005260:Female; D019942:Genes, p16 / Q000502:physiology*; D018095:Germ-Line Mutation; D006801:Humans; D008297:Male; D008545:Melanoma / Q000235:genetics*; D008875:Middle Aged; D010190:Pancreatic Neoplasms / Q000235:genetics; D010375:Pedigree; D016133:Polymerase Chain Reaction; D012878:Skin Neoplasms / Q000235:genetics*
D017931:DNA Primers; D004273:DNA, Neoplasm