Molecular alterations at chromosome 9p21 in melanocytic nevi and melanoma.

Background The chromosome 9p21 and its CDKN locus, with the p16 tumour suppressor
gene (CDKN2A), are recognized as the genomic regions involved in the
pathogenesis of melanoma.
Objectives To elucidate further the role of such regions during the different phases
of melanocytic tumorigenesis.
Methods Tissue sections from naevi, primary and metastatic melanomas were investigated
by fluorescence in situ hybridization for allelic loss at the 9p21 chromosome
and by immunochemistry for p16CDKN2A expression.
Results Dysplastic naevi and primary or secondary melanomas were found to carry
hemizygous deletions within the entire 9p21 region at similar frequencies (varying
from 55% to 62%). Allelic deletion spanning the CDKN locus was observed
at significantly increased rates moving from early (7%) to advanced (28%) primary
melanomas and to secondary melanoma lesions (37%) (P = 0Æ018). Also,
inactivation of the p16 gene (CDKN2A) was absent in naevi and present at steadily
increasing rates moving from primary melanomas (7% early lesions to 17%
advanced lesions) to melanoma metastases (62%) (P = 0Æ004).
Conclusions Our findings indicate that, in a model of sequential accumulation of
genetic alterations, 9p21 deletions may play a role in melanocytic transformation
and tumour initiation whereas rearrangements at the CDKN locus, and p16 gene
(CDKN2A) inactivation may contribute to tumour progression