Abnormalities of chromosomes 3 and 8 in posterior uveal melanoma correlate with prognosis

Abstract

Posterior uveal melanomas have nonrandom alterations affecting chromosomes 3, 6, and 8. Loss of chromosome 3 in uveal melanoma has been shown to act as a predictor of disease‐free and overall survival. To confirm the significance of chromosome 3 loss and to extend the observations to include those of the associated alterations of chromosome 8, we have conducted a cytogenetic analysis on a series of 42 tumours from patients with primary uveal melanoma who were followed up for a median of 31 months (range = 8‐96 months). Abnormalities of chromosomes 3 and 8 were the commonest changes and were confirmed in 10 tumours using flourescence in situ hybridization. Monosomy of chromosome 3 was found in 21 (50%) of the tumours, and 23 (54%) tumours had additional copies of 8q. Alterations of chromosomes 3 and 8 were found occurring together in 19 (45%) of the tumours and were significantly associated with a ciliary body component (P < 0.0001). Prognostic indicators and changes of chromosomes 3 and 8 were analysed for correlation with patient survival. Of the chosen parameters, only ciliary body involvement (P = 0.003), monosomy of chromosome 3 (P = 0.0007), and additional copies of 8q (P = 0.003) correlated with reducted survival. Evaluation of the dosage effect of additional copies of chromosome arm 8q showed a significant association with reduced survival (P = 0.0001), which was also predictive of a decreased disease‐free interval (P = 0.01). Thus, the cytogenetic analysis of uveal melanoma may provide a valuable predictor of prognosis. Genes Chromosom. Cancer 19:22–28, 1997. © 1997 Wiley‐Liss, Inc.

Assessment of genomic instability in breast cancer and uveal melanoma by random amplified polymorphic DNA analysis

“…24,29,30 Emphasis has been given lately to the monosomy of chromosome 3 since it has been correlated with metastasis and poor prognosis. 31,32 The finding that this monosomy is the most frequent aberration suggests the presence of tumor-suppressor genes on this chromosome. Cytogenetic studies and microsatellite analysis were used to restrict the candidate regions for these genes, suggesting that loci 3q24-q26 and 3p25 might harbor them.…”

Multiple locations on chromosome 3 are the targets of specific deletions in uveal melanoma

“…9 The description of cytogenetic abnormalities seen in this study was reported using the International System of Human Cytogenetic Nomenclature (ISCN, 1995). To identify the abnormalities detected by molecular genetic findings, FISH was performed using chromosome 3-specific paints as outlined previously.…”

“…To identify the abnormalities detected by molecular genetic findings, FISH was performed using chromosome 3-specific paints as outlined previously. 9 Slides were analysed on an Olympus BX50 microscope linked to a CCD camera, and analysed using MacProbe software (PSI Inc.).…”

“…[5][6][7] Monosomy 3 is present in approximately 50% of tumours and is associated with a poor prognosis. [8][9][10] Postoperative observation of cases with monosomy 3 showed that 57% of cases developed metastasis within 3 years. 11 In contrast, tumours with disomy 3 rarely metastasise.…”

“…11 Confirmation of monosomy 3 as a highly sensitive prognostic indicator is supported by other studies, in which its association with a gain of chromosome 8q confers a poor prognosis. 9 The recurrent loss of chromosomal regions in tumours indicates the possible location of a tumour suppressor gene (TSG), which can be identified by the detailed mapping of deleted regions. 12 Deletions of chromosome 3 are frequently observed in many tumour types, although such abnormalities tend to affect only chromosome 3p, with 3q deletions being a relatively rare event.…”