Chromosomal aberrations defining uveal melanoma of poor prognosis

doi:10.1016/0140-6736(92)90861-V

The Lancet

Volume 339, Issue 8794, 14 March 1992, Pages 691-692

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References (8)

Jm Seddon et al.
Comparison of survival rates for patients with uveal melanoma after treatment with proton beam irradiation or enucleation
Am J Ophthalmol
(1985)
Jm Seddon et al.
Relative survival rates after alternative therapies for uveal melanoma
Ophthalmology
(1990)
De Horsman et al.
Monosomy 3 and isochromosome 8q in a uveal melanoma
Cancer Genet Cytogenet
(1990)
Ca Griffin et al.
Tnsomy 7p in an ocular melanoma
Surv Ophthalmol
(1988)

There are more references available in the full text version of this article.

Cited by (74)

Choroidal and ciliary body melanoma, the Zimmerman hypothesis
2023, Ophthalmic Pathology: The Evolution of Modern Concepts
In 1978, Lorenz Zimmerman and colleagues published a paper in the British Journal of Ophthalmology with the title “Does enucleation of the eye containing a malignant melanoma prevent or accelerate the dissemination of tumor cells?” The paper had been rejected by an American journal but found a forum elsewhere. The argument that surgery accelerated tumor dissemination was straightforward. The paper came at the same time that ocular oncologists were debating whether brachytherapy (radiation) was as effective as surgical enucleation. The Zimmerman hypothesis cast a shadow over the role of management of uveal melanoma. The Collaborative Ocular Melanoma Study was an outgrowth of these reservations. It was the largest National Eye Institute study to that time. During its course, a revolution in molecular biology would alter how the prognosis for melanoma was determined. The photograph gallery includes a uveal melanoma neglected for 30 years as well as the pathology of melanomas treated by surgical enucleation and vitrectomy.
Translation of single-cell transcriptomic analysis of uveal melanomas to clinical oncology
2021, Progress in Retinal and Eye Research
Citation Excerpt :
Several other clinical and histological features are used to complement the conventional AJCC UM staging and patient prognosis (Kaliki et al., 2015; Mäkitie et al., 1999) (Fig. 1). However, a major twist came from cytogenetic studies identifying that the recurrent loss of chromosome 3 and gain of chromosome 8q in tumours (Horsman et al., 1990; Prescher et al., 1992; Sisley et al., 1990) were associated with poor prognosis tumours (Damato et al, 2007, 2009; Jager et al., 2020; Pandiani et al., 2017; Smit et al., 2020; Trolet et al., 2009). Adding chromosome status together with the AJCC resulted in an even better system (Bagger et al., 2015).
Uveal melanoma (UM) is an aggressive and deadly neoplasm. In recent decades, great efforts have been made to obtain a more comprehensive understanding of genetics, genomics and molecular changes in UM, enabling the identification of key cellular processes and signalling pathways. Still, there is no effective treatment for the metastatic disease. Intratumoural heterogeneity (ITH) is thought to be one of the leading determinants of metastasis, therapeutic resistance and recurrence. Crucially, tumours are complex ecosystems, where cancer cells, and diverse cell types from their microenvironment engage in dynamic spatiotemporal crosstalk that allows cancer progression, adaptation and evolution. This highlights the urgent need to gain insight into ITH in UM and its intersection with the microenvironment to overcome treatment failure. Here we provide an overview of the studies and technologies to study ITH in human UMs and tumour micro-environmental composition. We discuss how to incorporate ITH into clinical consideration for the purpose of advocating for new clinical management. We focus on the application of single-cell transcriptomic analysis and propose that understanding the driving forces and functional consequences of the observed tumour heterogeneity holds promise for changing the treatment paradigm of metastatic UMs, surmounting resistance and improving patient prognosis.
Genetic Analysis of Uveal Melanoma in 658 Patients Using the Cancer Genome Atlas Classification of Uveal Melanoma as A, B, C, and D
2019, Ophthalmology
The Cancer Genome Atlas (TCGA) classification has been validated for uveal melanoma (UM) prognostication. We applied TCGA classification to UM biopsied using fine-needle aspiration biopsy (FNAB) to determine the predictability for metastasis and death.
Retrospective cohort study.
Patients with UM treated with plaque radiotherapy at Wills Eye Hospital, Philadelphia, Pennsylvania, from October 1, 2008, through December 31, 2018, who completed genetic analysis of chromosomes 3 and 8 after FNAB.
Tumors were classified as A, B, C, or D and were compared using the chi-square test, Fisher exact test, analysis of variance, and Kaplan-Meier analysis.
Metastasis and death.
Six hundred fifty-eight UM patients were categorized accordingly as TCGA class A (n = 342 [52%]), B (n = 91 [14%]), C (n = 118 [18%]), and D (n = 107 [16%]). More advanced tumor classification revealed older mean patient age (56 vs. 53 vs. 60 vs. 63 years, respectively; P < 0.001), worse presenting visual acuity (20/20–20/50: 81% vs. 67% vs. 71% vs. 66%, respectively; P < 0.001), greater distance from the optic disc (3.5 vs. 4.9 vs. 5.7 vs. 5.3 mm, respectively; P < 0.001), larger tumor basal diameter (10.3 vs. 12.9 vs. 13.9 vs. 15.3 mm, respectively; P < 0.001), and greater tumor thickness (4.3 vs. 6.1 vs. 6.6 vs. 7.5 mm, respectively; P < 0.001). After mean follow-up (47.6 vs. 47.6 vs. 42.9 vs. 28.7 months, respectively; P < 0.001), more advanced TCGA class was associated with increased risk of metastasis (3% vs. 10% vs. 25% vs. 41%, respectively; P < 0.001) and death (1% vs. 0% vs. 3% vs. 9%, respectively; P < 0.001). Compared with class A, the 5-year hazard ratio for metastasis increased at 4.1 (B vs. A; P = 0.01), 10.1 (C vs. A; P < 0.001), and 30.0 (D vs. A; P < 0.001). The 5-year hazard ratio for death increased at 3.1 (C vs. A; P = 0.11) and 13.7 (D vs. A; P < 0.001) with no deaths in class B.
Grouping of UM using TCGA classification predicts the risk of melanoma-related metastasis and death.
Variability of Bad Prognosis in Uveal Melanoma
2019, Ophthalmology Retina
Survival of patients with uveal melanoma classified to have a bad prognosis.
To explore reasons for reported variability in survival of patients with uveal melanoma classified to have a bad prognosis.
We searched PUBMED, MEDLINE, and EMBASE for studies reporting survival data for uveal melanoma undergoing prognostic testing with chromosome 3 status by fluorescence in situ hybridization (FISH), comparative genomic hybridization (CGH), microsatellite analysis (MSA), multiplex ligation-dependent probe amplification (MLPA), single nucleotide polymorphism (SNP), gene expression profiling (GEP) class, and exon sequencing. Only studies reporting 1-year, 3-year, or 5-year survival were included in the study.
The initial search resulted in 49 studies. Only 12 studies met inclusion criteria. Three studies reported survival data for FISH, 1 study reported survival data for CGH, 1 study reported survival data for MSA, 3 studies reported survival data for MLPA, 3 studies reported survival data for SNP, 3 studies reported survival data for GEP, and 2 studies reported survival data for a combination of tests. No studies reported survival data for exon sequencing. Six studies reported percent free of metastatic death, 2 studies reported metastasis-free survival (MFS), 2 studies reported overall survival (OS), and 2 studies reported probability of metastasis. Metastasis-free survival (5 years) for monosomy 3 by FISH was 40% to 60%, by MLPA was 30% to 40%, by SNP was 72%, and for GEP class 2 was not reported. Overall survival (5 years) for monosomy 3 and disomy 8 tumors by MLPA and GEP class 2 were not comparable (81% and 55%, respectively).
Variability exists in reported survival for uveal melanoma with a bad prognosis. Several factors, including composition of study population (tumor size, exclusion of iris melanoma, duration of median follow-up), method of obtaining tumor sample, type of prognostic test, and use of variable outcome measures, can explain some of the observed differences in survival. Variations in determining the cause of death (metastatic or nonmetastatic) may be the major reason for the observed differences. Standardization of study methods and outcome measures will allow comparison of survival data derived from different prognostic tests.
Personalized Prognosis of Uveal Melanoma Based on Cytogenetic Profile in 1059 Patients over an 8-Year Period: The 2017 Harry S. Gradle Lecture
2017, Ophthalmology
To determine the personalized rate of uveal melanoma–related metastasis on the basis of individual tumor cytogenetic profile.
Retrospective case series.
A total of 1059 patients with uveal melanoma.
Fine-needle aspiration biopsy (FNAB) for DNA amplification and whole genome array–based assay were performed for analysis of chromosomes 3, 6, and 8.
Melanoma-related metastasis.
The mean patient age was 57 years, and most were white (1026/1059, 97%). The melanoma involved the choroid (938/1059, 89%), ciliary body (85/1059, 8%), or iris (36/1059, 3%), with 19% being macular in location. The mean largest basal diameter was 11 mm (median, 12 mm; range, 3–24 mm), and mean thickness was 5 mm (median, 4 mm; range, 1–20 mm). On the basis of individual chromosomal mutations, risk for metastasis was increased for chromosome 3 partial monosomy (hazard ratio [HR], 2.84; P = 0.001), 3 complete monosomy (HR, 6.7, P < 0.001), 6q loss (HR, 3.1, P = 0.003), 8p loss (HR, 21.5, P < 0.001), and 8q gain (HR, 9.8, P < 0.001). Kaplan–Meier estimate for melanoma-related metastasis in 1, 3, 5, and 7 years for 3 partial monosomy was 1%, 5%, 14%, and 17%; for 3 complete monosomy was 3%, 19%, 28%, and 37%; for 6q loss was 8%, 23%, 49%, and 49%; for 8p loss was 8%, 29%, not estimable (NE), and NE; and for 8q gain was 6%, 21%, 35%, 48%, respectively. On the basis of personalized cytogenetic profiles, Kaplan–Meier estimates (1, 3, and 5 years) for melanoma-related metastasis for 3, 6, and 8 disomy (1%, 1%, 4% [HR, 1]) were low compared with the higher-risk combinations of 3 complete monosomy, 6p gain, and 8q gain (0%, 29%, 29% [HR, 10.6, P = 0.02]); 3 complete monosomy, 6 disomy, 8q gain, and 8p gain (14%, 14%, NE [HR, 18.3, P = 0.02]); 3 complete monosomy, 6 disomy, and 8q gain (8%, 27%, 39% [HR, 19.5, P < 0.001]); and 3 complete monosomy, 6 disomy, 8q gain, and 8p loss (3%, 28%, NE [HR, 31.6, P < 0.001]), respectively.
Risk for melanoma-related metastasis strongly correlates with personalized cytogenetic profiles, with 5-year Kaplan–Meier estimates ranging from 4% with chromosomes 3, 6, and 8 disomy up to 39% for 3 complete monosomy, 6 disomy, and 8q gain.
Update on Tumor-Node-Metastasis Staging for Uveal Melanoma
2016, Advances in Ophthalmology and Optometry
Citation Excerpt :
Among these, loss of 1 copy of chromosome 3 (known as monosomy 3) has emerged as a powerful predictor of metastatic risk. Monosomy 3, which can be detected using a variety of techniques, is found in the majority of metastasizing uveal melanoma [17–21]. Gene expression profiling also has been developed for uveal melanoma risk stratification.

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LETTERS to the EDITORChromosomal aberrations defining uveal melanoma of poor prognosis

Am J Ophthalmol

Ophthalmology

Cancer Genet Cytogenet

Surv Ophthalmol

LETTERS to the EDITOR
Chromosomal aberrations defining uveal melanoma of poor prognosis