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Unformatted text preview: ies in melanoma
All studies on chromosomal aberrations, from cytogenetics to CGH analysis, show a
noticeable diversity in genomic aberrations, reflecting the heterogeneous nature of
CMM. Some of the aberrations are listed below.
Sporadic dysplastic nevi show a high rate of loss of heterozygosity of chromosomes
1p and 9q31; some variants show a predominant allelic deletion at chromosome 9p21
(INK4 locus). In sporadic melanomas, chromosomes 1, 6, 7, 9, and 10 are most
commonly affected. In chromosome 1, structural rearrangements are frequent and
include translocations or deletions of 1p12–22.3, loss of heterozygosity in 1p3, and
deletion of 1p36.3 (61). In addition, one study found a linkage to chromosome 1p36
(61). The abnormalities in chromosome 7 consist of chromosomal losses or gains,
with the latter associated with increased expression of the receptor for epidermal
growth factor located on 7p12-13 (62). Loss of chromosome 10 is frequently
associated with melanoma progression, possibility related to loss of the NMA
(neuromedin A) gene, located at 10p11.2-12.3, which is a potential inhibitor of
metastatic capability (63).
The results of array-based comparative genomic hybridization (array-CGH) analyses
of melanocytic neoplasms have shown different patterns of chromosomal aberrations
17 in benign melanocytic nevi and melanoma. In melanomas the genetic alterations
depended on anatomical site, Clark’s histogenetic type, and sun-exposure pattern.
Melanomas on acral sites have significantly more aberrations involving chromosomes
5p, 11q, 12q, and 15, as well as focused gene amplifications. Melanomas classified as
lentigo malignant melanomas or occurring on severely sun-damaged skin showed
markedly more frequent losses of chromosomes 17p and 13q (48). A recent genomewide study in melanocytic lesions, using array-CGH, showed the most common
overlapping regions with losses were mapped to 9p24.3-q13, 10 and 11q14.1-qter,
whereas copy number gains were most frequent on chromosomes 1q, 7, 17q and 20q.
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