Translating Uveal Melanoma Cytogenetics Into Clinical Care

Damato, Bertil; Coupland, Sarah E.

doi:10.1001/archophthalmol.2009.40

Cited by 84 publications

(55 citation statements)

References 22 publications

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“…Indeed, it has been postulated that monosomy 3 tumor cells in heterogeneous tumors can be masked from detection by the more numerous disomy 3 cells. 16 We investigated the effect intratumoral genetic heterogeneity on the 15-gene assay in two ways. First, we compared the expression profile of the 12 discriminating genes in eight fresh frozen tumor samples and matched postenucleation FNAB samples from the same tumor.…”

Section: Effect Of Tumor Heterogeneity On Gene Expression Profilementioning

confidence: 99%

An Accurate, Clinically Feasible Multi-Gene Expression Assay for Predicting Metastasis in Uveal Melanoma

Onken

Worley

Tuscan

et al. 2010

The Journal of Molecular Diagnostics

308

275

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Uveal (ocular) melanoma is an aggressive cancer that often forms undetectable micrometastases before diagnosis of the primary tumor. These micrometastases later multiply to generate metastatic tumors that are resistant to therapy and are uniformly fatal. We have previously identified a gene expression profile derived from the primary tumor that is extremely accurate for identifying patients at high risk of metastatic disease. Development of a practical clinically feasible platform for analyzing this expression profile would benefit high-risk patients through intensified metastatic surveillance , earlier intervention for metastasis , and stratification for entry into clinical trials of adjuvant therapy. Here , we migrate the expression profile from a hybridization-based microarray platform to a robust , clinically practical , PCR-based 15-gene assay comprising 12 discriminating genes and three endogenous control genes. We analyze the technical performance of the assay in a prospective study of 609 tumor samples , including 421 samples sent from distant locations. We show that the assay can be performed accurately on fine needle aspirate biopsy samples , even when the quantity of RNA is below detectable limits. Preliminary outcome data from the prospective study affirm the prognostic accuracy of the assay. This prognostic assay provides an important addition to the armamentarium for managing patients with uveal melanoma , and it provides a proof of principle for the development of similar assays for other cancers.

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Section: Effect Of Tumor Heterogeneity On Gene Expression Profilementioning

confidence: 99%

An Accurate, Clinically Feasible Multi-Gene Expression Assay for Predicting Metastasis in Uveal Melanoma

Onken

Worley

Tuscan

et al. 2010

The Journal of Molecular Diagnostics

308

275

View full text Add to dashboard Cite

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“…[21][22][23] Genetic prognostication Genetic analysis provides the single best estimate for the risk of metastasis from uveal melanoma. 12,24,25 Such an analysis can be performed by charting chromosomal alternations 26,27 or by gene expression profiling. 24,25,28 The latest TNM edition encourages recording of genetic features.…”

Section: Prognosis Of the Primary Tumourmentioning

confidence: 99%

Prognostication in eye cancer: the latest tumor, node, metastasis classification and beyond

Kivelä

Kujala

2012

Eye

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The tumour, node, metastasis (TNM) classification is a universal cancer staging system, which has been used for five decades. The current seventh edition became effective in 2010 and covers six ophthalmic sites: eyelids, conjunctiva, uvea, retina, orbit, and lacrimal gland; and five cancer types: carcinoma, sarcoma, melanoma, retinoblastoma, and lymphoma. The TNM categories are based on the anatomic extent of the primary tumour (T), regional lymph node metastases (N), and systemic metastases (M). The T categories of ophthalmic cancers are based on the size of the primary tumour and any invasion of periocular structures. The anatomic category is used to determine the TNM stage that correlates with survival. Such staging is currently implemented only for carcinoma of the eyelid and melanoma of the uvea. The classification of ciliary body and choroidal melanoma is the only one based on clinical evidence so far: a database of 7369 patients analysed by the European Ophthalmic Oncology Group. It spans a prognosis from 96% 5-year survival for stage I to 97% 5-year mortality for stage IV. The most accurate criterion for prognostication in uveal melanoma is, however, analysis of chromosomal alterations and gene expression. When such data are available, the TNM stage may be used for further stratification. Prognosis in retinoblastoma is frequently assigned by using an international classification, which predicts conservation of the eye and vision, and an international staging separate from the TNM system, which predicts survival. The TNM cancer staging manual is a useful tool for all ophthalmologists managing eye cancer. Keywords: conjunctival malignancies; eyelid malignancies; orbital malignances; retinoblastoma; uveal melanomaThe tumour, node, metastasis (TNM) classification is a cancer staging system, which has been in worldwide use across all medical specialties for five decades. 1 It emerged in 1968 when the International Union Against Cancer published the first edition of its classification based on the anatomic extent of the tumour after testing a set of draft classifications for 23 cancer sites. None of these sites related to the eye.Indeed, eye cancer is a latecomer in the TNM classification, appearing for the first time in the fourth and fifth editions. 2 The first ophthalmic section covered six sites and five cancer types-carcinoma and melanoma of the eyelid and conjunctiva, melanoma of the uvea, retinoblastoma, sarcoma of the orbit, and carcinoma of the lacrimal gland-but these classifications were untested and were rarely used outside cancer registries.The ophthalmic section was revised for the sixth edition of TNM in 2002. 3 This edition was based on the published literature, but the classifications were not tested against clinical data. The revision received publicity 4 but did not make a breakthrough. Meanwhile, data were collected of other cancers to improve staging. For the updated TNM classification of cutaneous melanoma, data from over 20 000

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“…In 1999, we started offering genetic tumor typing to all patients treated by local resection or enucleation, using fluorescence in situ hybridization (FISH;15). This method lacked sensitivity, however, so that small chromosomal abnormalities were missed (16).…”

mentioning

confidence: 99%

Genotypic Profiling of 452 Choroidal Melanomas with Multiplex Ligation-Dependent Probe Amplification

Damato

Dopierała

Coupland

2010

Clinical Cancer Research

Self Cite

278

239

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Purpose: Metastasis from uveal melanoma occurs almost exclusively with tumors showing chromosome 3 loss. We used multiplex ligation-dependent probe amplification (MLPA) to detect chromosome 1p, 3, 6p, 6q, 8p, and 8q abnormalities in uveal melanomas. The purpose of this study was to correlate our MLPA results with other risk factors and metastatic death.Experimental Design: Patients were included if they had a uveal melanoma involving choroid. Correlations between baseline risk factors were analyzed using the chi-square test (without Yates's adjustment) and the Mann-Whitney test, with log-rank analysis for associations with metastatic death.Results: The patients (194 female; 258 male) had a median age of 59.4 years and a median follow-up of 1.89 years. MLPA abnormalities occurred in a wide variety of combinations. Ten-year disease-specific mortality was 0% in 133 tumors with no chromosome 3 loss, 55% in tumors with chromosome 3 loss but no chromosome 8q gain, and 71% in 168 tumors showing combined chromosome 3 loss and 8q gain. In tumors with both these abnormalities, epithelioid melanoma cytomorphology, closed loops, and high mitotic rate correlated with poor survival as did lack of chromosome 6p gain.Conclusions: These results support the use of MLPA for routine clinical prognostication, especially if the genetic data are considered together with clinical and histologic risk factors. We showed a wide variety of MLPA results, which suggests that chromosomal abnormalities in uveal melanoma accumulate in a variable sequence. Clin Cancer Res; 16(24); 6083-92. Ó2010 AACR.

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Translating Uveal Melanoma Cytogenetics Into Clinical Care

Cited by 84 publications

References 22 publications

An Accurate, Clinically Feasible Multi-Gene Expression Assay for Predicting Metastasis in Uveal Melanoma

An Accurate, Clinically Feasible Multi-Gene Expression Assay for Predicting Metastasis in Uveal Melanoma

Prognostication in eye cancer: the latest tumor, node, metastasis classification and beyond

Genotypic Profiling of 452 Choroidal Melanomas with Multiplex Ligation-Dependent Probe Amplification

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