Longitudinal Assessment of the Nevus Phenotype in a Melanoma Kindred

J Invest Dermatol. 2004 Sep;123(3):576-82. doi: 10.1111/j.0022-202X.2004.23312.x.


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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adolescent
  • Adult
  • Child
  • Cyclin-Dependent Kinase Inhibitor p16 / genetics*
  • Environment
  • Family Health
  • Female
  • Follow-Up Studies
  • Heterozygote
  • Humans
  • Longitudinal Studies
  • Male
  • Melanoma / genetics*
  • Middle Aged
  • Nevus / genetics*
  • Phenotype
  • Point Mutation
  • Skin Neoplasms / genetics*


  • Cyclin-Dependent Kinase Inhibitor p16