PURPOSE. To investigate the presence of focal or diffuse heterogeneity of monosomy 3 in uveal melanoma, by using fluorescence in situ hybridization (FISH). METHODS. Direct interphase FISH in a series of 151 uveal melanomas revealed 82 tumors with loss of chromosome 3. Tumors with monosomy 3 were suspected to be heterogeneous if there were low percentages of monosomy 3, triploid clones, inconsistencies between FISH on centromere 3 and the long arm of chromosome 3, or discrepancies between fine-needle-aspiration biopsies (FNABs) and the main tumor. These tumors (n = 16), all choroidal melanomas, were selected and analyzed for intratumor heterogeneity by using FISH on paraffin-embedded tissue sections. RESULTS. Different sections of each tumor were evaluated with FISH: 6 tumors showed monosomy 3 in the same percentage throughout the tumor, and 10 showed multiple clones with different percentages of monosomy 3. However, these tumors did not show focal heterogeneity with respect to chromosome 3 status, and differences in monosomy 3 distribution between the base and apex of the tumor could not be identified. CONCLUSIONS. Although a small number of uveal melanomas show heterogeneity for chromosome 3, it does not affect survival. In the presence of triploid clones, the loss of chromosome 3 is more difficult to interpret. In general, tumor biopsies in uveal melanoma provide an accurate prediction of the patient's prognosis. Copyright

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Persistent URL dx.doi.org/10.1167/iovs.08-2279, hdl.handle.net/1765/27237
Journal Investigative Ophthalmology & Visual Science
Mensink, H.W, Vaarwater, J, Kiliç, E, Naus, N.C, Mooy, N, Luyten, G.P.M, … de Klein, J.E.M.M. (2009). Chromosome 3 intratumor heterogeneity in uveal melanoma. Investigative Ophthalmology & Visual Science, 50(2), 500–504. doi:10.1167/iovs.08-2279