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Andrea G. M. Scholes, Triantafillos Liloglou, Paul Maloney, Suzanne Hagan, Janice Nunn, Paul Hiscott, Bertil E. Damato, Ian Grierson, John K. Field; Loss of Heterozygosity on Chromosomes 3, 9, 13, and 17, Including the Retinoblastoma Locus, in Uveal Melanoma. Invest. Ophthalmol. Vis. Sci. 2001;42(11):2472-2477.
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purpose. To identify tumor-suppressor loci that may contribute to the
pathogenesis of uveal melanoma.
methods. Multiplex fluorescence microsatellite assays were performed on 27 uveal
melanomas using markers at 3p25-p26, 3p14.2, 9p21-p23, 13q14,
13q12.3-q13, and 17p13, close to or within the von Hippel Lindau
(VHL), fragile histidine triad (FHIT),
p16/cyclin-dependent kinase inhibitor 2 (CDKN2A),
retinoblastoma (RB1), breast cancer 2
(BRCA2), and p53 tumor suppressor loci,
respectively. Further markers on chromosomes 3 and 9 were analyzed
results. Loss of heterozygosity (LOH) was identified in 63% of tumors, most
frequently on chromosome 3 (52%), in association with epithelioid
cells (P = 0.0002) and microvascular loops
(P = 0.0008). In the majority of cases, LOH on
chromosome 3 was detected at all informative markers. The second most
common alteration was LOH at an RB1 intragenic marker
(21% tumors), with retention of a more centromeric 13q marker (near BRCA2). The pattern of LOH on chromosome 9p was
consistent with the involvement of a region telomeric to CDKN2A. LOH at TP53 was infrequent.
conclusions. In the majority of cases, chromosome 3 LOH involves an entire
chromosome homologue, which hampers identification of the relevant
suppressor loci. This LOH correlates with the presence of
microvascular loops and epithelioid cells, two of the recognized
histologic indicators of poor prognosis. Data for chromosomes
13 and 9 support a role for RB1 in the
pathogenesis of uveal melanoma but also raise the possibility
of the involvement of additional loci close to RB1 and CDKN2A.
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