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Yan Aalto, Lotta Eriksson, Stefan Seregard, Olle Larsson, Sakari Knuutila; Concomitant Loss of Chromosome 3 and Whole Arm Losses and Gains of Chromosome 1, 6, or 8 in Metastasizing Primary Uveal Melanoma. Invest. Ophthalmol. Vis. Sci. 2001;42(2):313-317.
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purpose. To elucidate the genetic differences between metastasizing and
nonmetastasizing primary tumors, uveal melanoma samples were screened
for DNA copy number alterations by comparative genomic hybridization
methods. DNA copy number changes were studied on 14 primary uveal melanomas that
had not metastasized, 15 primary uveal melanomas that had metastasized,
and on 6 metastases that were available from 6 primary uveal melanomas.
CGH is based on quantitation of the fluorescence intensity of
differentially labeled DNAs. Tumor DNA labeled with FITC dCTP and dUTP
and normal DNA labeled with Texas red dCTP and dUTP were hybridized to
normal metaphase chromosomes. The hybridizations were analyzed using an
Olympus fluorescence microscope and the ISIS digital image analysis
system to identify gain or loss of genetic material.
results. Primary uveal melanomas that had metastasized and metastases had
significantly more changes than primary uveal melanomas that had not
metastasized. Comparison between primary nonmetastasizing tumors,
metastasizing tumors, and metastases showed that the most common DNA
copy number changes were −3 (21%, 73%, 67%, respectively), −6q
(7%, 40%, 83%), −1p (0, 33%, 33%), −13q (14%, 13%, 50%), −8p
(14%, 27%, 0), −18 (7%, 13%, 33%), +8q (14%, 53%, 100%), +6p
(29%, 20%, 17%), +1q (0, 7%, 33%), and +16p (0, 7%, 33%).
conclusions. Loss of chromosome 3, loss of 6q, and gain of 8q were significantly
associated with poor overall survival. In addition, losses of 1p were
only found in primary uveal melanomas that had metastasized and in
metastases, which suggests that this region may harbor a tumor
suppressor gene important in the tumor progression. Finally, loss of
chromosome 3 may be associated with isochromosome formation of 1q, 6p,
8q, 16p, 20q, and 22q.
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