Genomic Investigations of Posterior Uveal Melanoma

Hovland, Peter; Trempe, Clement L.

doi:10.1080/08820530500350522

Cited by 4 publications

(3 citation statements)

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“…Biological verification for the role of 1 gene, ID2 , in the aggressive uveal melanoma phenotype was established via transgenic crosses. Additional candidate genes were revealed in these studies, and others are likely to exist, based on the results of cytogenetic changes associated with UM, including monosomy 3, 6p, deletions of 3p25.1–3p25.2, and gains at 8q (Hovland and Trempe, 2005).…”

Section: Case Reportmentioning

confidence: 92%

“…In transgenic mice, forced expression of the human HRAS G12V oncogene in melanocytic cells using a recombinant tyrosinase promoter generates melanoma-prone strains that develop mixed pigmented ocular tumors derived from retinal pigment epithelium and melanocytes of the uveal tract (Kramer et al, 1998). Inactivation of the CKDN2A tumor suppressor gene (i.e., Ink4a/Arf gene) is also associated with cutaneous and uveal melanomas (de Snoo and Hayward, 2005; Hovland and Trempe, 2005). Via shared exons 2 and 3, but with separate promoters and first exons, the CKDN2A gene encodes 2 tumor suppressor proteins, p16Ink4a and p14Arf (p19Arf in mice) that regulate the retinoblastoma and P53 signaling pathways, respectively.…”

Section: Introductionmentioning

confidence: 99%

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Two Cases of Uveal Amelanotic Melanoma in Transgenic Tyr-HRAS+ Ink4a/Arf Heterozygous Mice

Latendresse

Muskhelishvili²,

Warbritton³

et al. 2007

Toxicol Pathol

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Uveal melanoma (UM) is uncommon among wild type mice. Efforts to develop transgenic mice to study this disease have resulted in pigmented tumors derived from the retinal pigment epithelium (RPE) or mixed tumors of RPE and UM complicating the study of UM specifically. Reported here are two early stage intraocular amelanotic melanomas discovered in 2 Tyr-HRAS+ Ink4a/Arf heterozygous (1 normal CKDN2A allele) transgenic FVB/n mice. These tumors were morphologically and immunohistochemically similar to spontaneous UM recently reported in the Ink4a/Arf homozygous (CKDN2A knockout) parent strain. The tumors originated in the posterior uveal tract. The neoplasms were comprised of bundles of spindle-shaped melanocytes admixed with some epithelioid cells. Tumors were immunohistochemically positive for neuron-specific enolase, S-100, pan-ras, but negative for cytokeratin and Melan-A. The development of early lenticular opacity and bilateral cataracts is a consistent phenotype of transgenic mice in which the retinoblastoma signaling pathway has been disrupted. Lenticular opacity and cataracts are rarely observed clinically in Tyr-HRAS+ Ink4a/Arf heterozygotes, rendering this strain suitable for ophthalmoscopy. Consequently, Tyr-HRAS+ Ink4a/Arf heterozygotes provide practical advantages, compared to the cataract-prone CKDN2A knockout strains, for real-time ophthalomoscopic detection and monitoring of UM while developing chemotherapeutic regimens and other research to understand the biology of UM.

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Section: Case Reportmentioning

confidence: 92%

Section: Introductionmentioning

confidence: 99%

Two Cases of Uveal Amelanotic Melanoma in Transgenic Tyr-HRAS+ Ink4a/Arf Heterozygous Mice

Latendresse

Muskhelishvili²,

Warbritton³

et al. 2007

Toxicol Pathol

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“…Uveal melanoma (UM) is an intraocular malignant tumor occurring mainly in adult Caucasian and originates from melanocytes of the choroid, iris, and ciliary body [1], [2]. Most of UMs (95%) are posterior UM (locating in the ciliary body and choroid).…”

Section: Introductionmentioning

confidence: 99%

A Comparative Transcriptomic Analysis of Uveal Melanoma and Normal Uveal Melanocyte

Wan

Zhou

et al. 2011

PLoS ONE

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BackgroundUveal melanoma is the most common primary intraocular tumor in adults in western countries. It is associated with very severe visual morbidity and may lead to distant metastases even after successful treatment of the primary tumor. In order to gain better insight into molecular mechanisms related to tumorigenesis and metastasis of uveal melanoma, we used next-generation sequencing technology (SOLiD, Life Technologies) to acquire global transcriptome alteration between posterior uveal melanoma cells and normal uveal melanocyte.ResultsFrom mRNAs of the cultured uveal melanoma cells and normal uveal melanocytes, we annotated more than 3.7×107 and 2.7×107 sequencing tags based on human Ensembl databases, respectively. For detailed analysis, we chose 5155 well-annotated genes mainly involved in the MAPK signaling pathway, cell cycle, cell adhesion junction, apoptosis, and P53 signaling pathways as well as melanogenesis. In an effort to confirm the authenticity of our sequencing results, we validated twenty-one identically differentially expressed genes by using quantitative real time PCR from cultured cell lines of other posterior uveal melanoma cells and normal uveal melanocytes.ConclusionWe have identified a large number of potentially interesting genes for biological investigation of uveal melanoma. The expression profiling also provides useful resources for other functional genomic and transcriptome studies. These 21 potential genes could discriminate between uveal melanoma cells and normal uveal melanocyte, which may be indicative of tumorigenesis process. Our results further suggest that high-throughput sequencing technology provides a powerful tool to study mechanisms of tumogenesis in the molecular level.

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Ocular Melanocytic Tumors

Yanoff

Sassani

2009

Ocular Pathology

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Genomic Investigations of Posterior Uveal Melanoma

Cited by 4 publications

References 46 publications

Two Cases of Uveal Amelanotic Melanoma in Transgenic Tyr-HRAS+ Ink4a/Arf Heterozygous Mice

Two Cases of Uveal Amelanotic Melanoma in Transgenic Tyr-HRAS+ Ink4a/Arf Heterozygous Mice

A Comparative Transcriptomic Analysis of Uveal Melanoma and Normal Uveal Melanocyte

Ocular Melanocytic Tumors

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