Chromosome 3 Intratumor Heterogeneity in Uveal Melanoma

• Published in: Investigative ophthalmology & visual science 2009-02, Vol.50 (2), p.500-504
• Main Authors: Mensink, Hanneke W, Vaarwater, Jolanda, Kilic, Emine, Naus, Nicole C, Mooy, Neeltje, Luyten, Gre, Bruggenwirth, Hennie T, Paridaens, Dion, de Klein, Annelies
• Format: Article
• Language: English
• Subjects: Biological and medical sciences; Choroid Neoplasms - genetics; Choroid Neoplasms - pathology; Chromosomes, Human, Pair 3 - genetics; Eye and associated structures. Visual pathways and centers. Vision; Female; Fundamental and applied biological sciences. Psychology; Genetic Heterogeneity; Humans; In Situ Hybridization, Fluorescence; Male; Medical sciences; Melanoma - genetics; Melanoma - pathology; Middle Aged; Monosomy - genetics; Monosomy - pathology; Ophthalmology; Prognosis; Tumors and pseudotumors of the eye, orbit, eyelid, lacrimal apparatus; Vertebrates: nervous system and sense organs
• ISSN: 0146-0404; 1552-5783; 1552-5783
• DOI: 10.1167/iovs.08-2279

To investigate the presence of focal or diffuse heterogeneity of monosomy 3 in uveal melanoma, by using fluorescence in situ hybridization (FISH). 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. 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. 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.