Longitudinal assessment of the nevus phenotype in a melanoma kindred.
Phenotypic characteristics of members of a melanoma prone kindred with a V126D CDKN2A gene mutation were monitored over approximately 15 y. Thirty-eight previously studied subjects were recruited. Participants underwent a complete skin examination by the same dermatologist who examined them initially. The size and location of all nevi were recorded on a body map diagram. Total nevus number (TNN) and total nevus density (TND) were determined. CDKN2A sequencing verified 13 mutation carriers and 16 non-carriers. Nine participants were spouse controls without a history of melanoma and did not carry a CDKN2A mutation. Mutation carriers demonstrated a greater mean TNN and TND at initial and follow-up examinations compared with non-carriers and continued to develop nevi rather than show nevus regression seen in non-carriers and spouse controls. Non-carriers showed an intermediate nevus phenotype between mutation carriers and spouse controls. Four of the 13 mutation carriers and one non-carrier have developed invasive melanoma. Over a 15-y interval, TNN and TND were increased in mutation carriers compared with non-carriers and spouse controls. Continued accumulation of nevi in mutation carriers supports a nevogenic role for this CDKN2A mutation. An intermediate nevus phenotype in non-carrier family members suggests the presence of additional modifier genes.
The Melanoma Program, Huntsman Cancer Institute, University of Utah, 2000 Circle of Hope, Salt Lake City, UT 84112-5550, USA.
Scott R
SR
Florell
Laurence J
LJ
Meyer
Kenneth M
KM
Boucher
Patricia A
PA
Porter-Gill
Marybeth
M
Hart
Jennica
J
Erickson
Lisa A
LA
Cannon-Albright
Lynn K
LK
Pershing
Ronald M
RM
Harris
Wolfram E
WE
Samlowski
John J
JJ
Zone
Sancy A
SA
Leachman
D000293:Adolescent; D000328:Adult; D002648:Child; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000235:genetics*; D004777:Environment; D005192:Family Health; D005260:Female; D005500:Follow-Up Studies; D006579:Heterozygote; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D008545:Melanoma / Q000235:genetics*; D008875:Middle Aged; D009506:Nevus / Q000235:genetics*; D010641:Phenotype; D017354:Point Mutation; D012878:Skin Neoplasms / Q000235:genetics*
D019941:Cyclin-Dependent Kinase Inhibitor p16