X inactivation, DNA deletion, and microsatellite instability in common acquired melanocytic nevi.
We have investigated several molecular characteristics of common acquired melanocytic nevi to clarify their relationship to malignant melanoma, which is characterized by clonality and the progressive accumulation of DNA deletions. Twenty-four common acquired nevi were subjected to analysis for loss of heterozygosity at four loci on chromosome 9p and six loci on 10q that are commonly deleted in melanoma, but no deletions were seen. X inactivation analysis was performed in lesions from females, using the methylation-sensitive restriction HpaII site in the CAG microsatellite repeat (HUMARA) in exon 1 of the androgen receptor (AR) gene. In 14 melanomas, 11 (92%) were confirmed to have skewed X inactivation, consistent with monoclonality, as were 16 (80%) of 20 benign nevi. One nevus (5%) and 4 (33%) of 12 melanomas also showed loss of heterozygosity at HUMARA. One nevus showed an additional allele, consistent with low level microsatellite instability, at one of the 11 loci that were examined. Common melanocytic nevi, therefore, arise by apparently clonal proliferation, but they do not share chromosomal deletions that are characteristic of melanoma. However, skewed X inactivation patterns were seen in some samples of adjacent microdissected normal epidermis.
Indsto
J O
JO
Westmead Institute for Cancer Research, University of Sydney at Westmead Millennium Institute, Darcy Road, Westmead, New South Wales 2145, Australia. James_Indsto@wmi.usyd.edu.au
Cachia
A R
AR
Kefford
R F
RF
Mann
G J
GJ
D002879:Chromosomes, Human, Pair 10; D002899:Chromosomes, Human, Pair 9; D004273:DNA, Neoplasm / Q000235:genetics; D005091:Exons; D005819:Genetic Markers; D006801:Humans; D019656:Loss of Heterozygosity; D008545:Melanoma / Q000235:genetics / Q000473:pathology; D018895:Microsatellite Repeats; D009508:Nevus, Pigmented / Q000235:genetics* / Q000473:pathology; D016133:Polymerase Chain Reaction; D011944:Receptors, Androgen / Q000235:genetics; D012189:Retrospective Studies; D017384:Sequence Deletion; D012867:Skin / Q000473:pathology; D012878:Skin Neoplasms / Q000235:genetics / Q000473:pathology; D018911:Trinucleotide Repeats; D014960:X Chromosome
D004273:DNA, Neoplasm; D005819:Genetic Markers; D011944:Receptors, Androgen