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J. P. Ehlers, L. Worley, M. D. Onken, J. W. Harbour; Overview of Cytogenetic Patterns and Alterations in 388 Primary Uveal Melanomas. Invest. Ophthalmol. Vis. Sci. 2007;48(13):4767.
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Several nonrandom chromosomal alterations have been described in uveal melanoma. However, most reports have examined only small numbers of tumor samples. In this study, we evaluated a large number of uveal melanomas to identify patterns of cytogenetic rearrangements that may provide new insights into tumorigenesis.
We evaluated chromosomal gains and losses in 50 primary uveal melanomas analyzed by array comparative genomic hybridization (CGH) in our laboratory, and 338 tumors examined by karyotypic analysis, CGH, fluorescence in-situ hybridization, or loss of heterozygosity in 13 peer-reviewed articles.
Chromosome 3 and 6 were reported for 316 tumors. Monosomy 3 occurred in 126 (39.9%) tumors, 6p gain in 78 (24.7%) tumors, and both alterations in 21 (6.6%) tumors. Chromosome 8q was evaluated in 364 tumors. Gain of 8q occurred in 98 (77.8%) tumors with monosomy 3, 49 (62.8%) tumors with 6p gain, and in 20 (21.7%) tumors with no alterations of chromosomes 3 or 6p. Gain of 8q occurred in the setting of 8p loss in 45% of monosomy 3 tumors and only 9% of tumors with gain of 6p (p<.001). Genomic instability was evaluated based on the percentage of aneuploidy found in 13 other chromosomes and chromosomal segments. Aneuploidy was present in 22% of the examined chromosomes in tumors with 8q gain and 7% of those chromosomes in tumors with normal 8q (p<.001).
Uveal melanomas tend to cluster cytogenetically into those with monosomy 3 and those with 6p gain. This large analysis confirms that both subtypes can exhibit gain of 8q, although interestingly the mechanism of 8q gain appears to be different between the two subtypes. We believe this is the first report to identify the association of 8q gain with generalized aneuploidy and genomic instability. These findings affirm the concept that there are two major genetic subtypes of uveal melanoma, which has important implications for tumor behavior and metastatic risk.
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