Alteration of chromosome 9p21 and/or p16 in benign and dysplastic nevi suggests a role in early melanoma progression (United States).
OBJECTIVE
The importance of p16 alterations in the pathogenesis of dysplastic nevi and sporadic melanoma remains controversial. The goal of this work was to discover if p16/9p21 alterations occur early in precursor lesions as well as related sporadic melanomas.


METHODS
DNA was microdissected from 44 cutaneous melanomas, 14 dysplastic nevi, and six nevi without atypia as part of a study of melanoma. Alteration of the p16 region on 9p21 was measured by loss of heterozygosity (LOH) analysis as well as detection of homozygous deletions for p16 exon 2.


RESULTS
This analysis revealed that LOH in 9p21 directly surrounding p16 occurred in approximately 40% (17/44) of melanoma tumors representing all Clark levels. LOH was also discovered in 64% (9/14) of dysplastic nevi, and 50% (3/6) of benign nevi. Homozygous deletion of p16 was found in 29% (4/14) of dysplastic nevi but never in benign nevi.


CONCLUSIONS
These studies reveal that LOH and homozygous deletion can affect 9p21 and the p16 locus early in putative precursor lesions of melanoma, even prior to the establishment of cytologically evident aberrant histology. Comparison of alterations in nevi and melanomas from the same individual revealed a pattern of progressive but heterogeneous events suggesting that systemic processes may affect this region of 9p21 at various times during melanoma progression.
Tran
Tina P
TP
Department of Anatomy, Virginia Commonwealth University, Richmond, USA.
Titus-Ernstoff
Linda
L
Perry
Ann E
AE
Ernstoff
Marc S
MS
Newsham
Irene F
IF
D000328:Adult; D000368:Aged; D001483:Base Sequence; D001707:Biopsy, Needle; D002872:Chromosome Deletion; D002899:Chromosomes, Human, Pair 9; D046508:Culture Techniques; D018450:Disease Progression; D005260:Female; D019942:Genes, p16; D005819:Genetic Markers; D006801:Humans; D016014:Linear Models; D019656:Loss of Heterozygosity / Q000235:genetics; D008297:Male; D008545:Melanoma / Q000235:genetics* / Q000473:pathology; D018895:Microsatellite Repeats / Q000235:genetics*; D008875:Middle Aged; D008969:Molecular Sequence Data; D009508:Nevus, Pigmented / Q000235:genetics* / Q000473:pathology; D016133:Polymerase Chain Reaction; D011336:Probability; D011379:Prognosis; D011446:Prospective Studies; D012042:Registries; D012680:Sensitivity and Specificity; D012878:Skin Neoplasms / Q000235:genetics* / Q000473:pathology; D014481:United States
D005819:Genetic Markers