The Cancer Genome Atlas Project: An Integrated Molecular View of Uveal Melanoma

Jager, Martine J.; Brouwer, Niels J.; Esmaeli, Bita

doi:10.1016/j.ophtha.2018.03.011

Cited by 81 publications

(84 citation statements)

References 25 publications

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“…Uveal Melanoma (UM) is the most common primary intraocular tumor in adults [ 1 , 2 ], and the second most common type of melanoma. It develops within the uveal tract of the eye, most frequently in the choroid [ 3 , 4 ].…”

Section: Introductionmentioning

confidence: 99%

Uveal Melanoma-Derived Extracellular Vesicles Display Transforming Potential and Carry Protein Cargo Involved in Metastatic Niche Preparation

Tsering

Laskaris

Abdouh

et al. 2020

Cancers

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Extracellular vesicles (EVs) carry molecules derived from donor cells and are able to alter the properties of recipient cells. They are important players during the genesis and progression of tumors. Uveal melanoma (UM) is the most common primary intraocular tumor in adults and is associated with a high rate of metastasis, primarily to the liver. However, the mechanisms underlying this process are poorly understood. In the present study, we analyzed the oncogenic potential of UM-derived EVs and their protein signature. We isolated and characterized EVs from five UM cell lines and from normal choroidal melanocytes (NCMs). BRCA1-deficient fibroblasts (Fibro-BKO) were exposed to the EVs and analyzed for their growth in vitro and their reprograming potential in vivo following inoculation into NOD-SCID mice. Mass spectrometry of proteins from UM-EVs and NCM-EVs was performed to determine a protein signature that could elucidate potential key players in UM progression. In-depth analyses showed the presence of exosomal markers, and proteins involved in cell-cell and focal adhesion, endocytosis, and PI3K-Akt signaling pathway. Notably, we observed high expression levels of HSP90, HSP70 and integrin V in UM-EVs. Our data bring new evidence on the involvement of UM-EVs in cancer progression and metastasis.

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Section: Introductionmentioning

confidence: 99%

Uveal Melanoma-Derived Extracellular Vesicles Display Transforming Potential and Carry Protein Cargo Involved in Metastatic Niche Preparation

Tsering

Laskaris

Abdouh

et al. 2020

Cancers

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“…Hence, in this study, we systematically evaluated the expression of alternative splicing events in 80 UM samples from the Cancer Genome Atlas (TCGA) dataset [16]. We identified some survival related AS events and biological pathways.…”

Section: Introductionmentioning

confidence: 99%

Alternative Splicing Events as Indicators for the Prognosis of Uveal Melanoma

Wan

Sang

Jin

et al. 2020

Genes

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Growing evidence has revealed that abnormal alternative splicing (AS) events are closely related to carcinogenic processes. However, the comprehensive study on the prognostic value of splicing events involved in uveal melanoma (UM) is still lacking. Therefore, splicing data of 80 UM patients were obtained from the Cancer Genome Atlas (TCGA) SpliceSeq and RNA sequence data of UM and patient clinical features were downloaded from the Cancer Genome Atlas (TCGA) database to identify survival related splicing events in UM. As a result, a total of 37996 AS events of 17911 genes in UM were detected, among which 5299 AS events of 3529 genes were significantly associated with UM patients’ survival. Functional enrichment analysis revealed that this survival related splicing genes are corelated with mRNA catabolic process and ribosome pathway. Based on survival related splicing events, seven types of prognostic markers and the final overall prognostic signature could independently predict the overall survival of UM patients. Finally, an 11 spliced gene was identified in the final signature. On the basis of these 11 genes, we constructed a Support Vector Machine (SVM) classifier and evaluated it with leave-one-out cross-validation. The results showed that the 11 genes could determine short- and long-term survival with a predicted accuracy of 97.5%. Besides, the splicing factors and alternative splicing events correlation network was constructed to serve as therapeutic targets for UM treatment. Thus, our study depicts a comprehensive landscape of alternative splicing events in the prognosis of UM. The correlation network and associated pathways would provide additional potential targets for therapy and prognosis.

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“…Likewise, the group of Vaquero-Garcia developed a model for personalized Prediction of Risk of Metastasis in UM (PRiMeUM) based on clinical and chromosomal information, showing 85% prediction accuracy [ 48 ]. Concomitantly, efforts were dedicated to the study of classifications solely based on genetic data [ 43 , 44 , 45 , 51 ]. Recently, The Cancer Genome Atlas (TCGA) classification has been proposed to improve the identification of high-risk patients for metastatic disease with respect to an AJCC-TNM clinical staging system [ 52 ].…”

Section: Prognosis Of Ummentioning

confidence: 99%

“…Specifically, the TCGA project, starting in 2005, was designed to conduct an expression analysis of mRNA, micro RNA, and long noncoding RNA and catalog genetic mutations of 33 different cancer types, including UM [ 53 ]. Based on TCGA results of chromosome 3 disomy or monosomy and degree of chromosome 8q gain, UM was categorized into 4 classes (A, B, C, and D) of progressive worsening prognosis [ 51 ]. Tumor clinical features and outcomes of metastatic risk and death were evaluated in a large sample of UM categorized on the basis of TCGA system, and the more advanced classes corresponded to older age, greater tumor size, and worst prognosis [ 54 ].…”

Section: Prognosis Of Ummentioning

confidence: 99%

Molecular Insights and Emerging Strategies for Treatment of Metastatic Uveal Melanoma

Mallone

Sacchetti

Moramarco

2020

Cancers

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Uveal melanoma (UM) is the most common intraocular cancer. In recent decades, major advances have been achieved in the diagnosis and prognosis of UM allowing for tailored treatments. However, nearly 50% of patients still develop metastatic disease with survival rates of less than 1 year. There is currently no standard of adjuvant and metastatic treatment in UM, and available therapies are ineffective resulting from cutaneous melanoma protocols. Advances and novel treatment options including liver-directed therapies, immunotherapy, and targeted-therapy have been investigated in UM-dedicated clinical trials on single compounds or combinational therapies, with promising results. Therapies aimed at prolonging or targeting metastatic tumor dormancy provided encouraging results in other cancers, and need to be explored in UM. In this review, the latest progress in the diagnosis, prognosis, and treatment of UM in adjuvant and metastatic settings are discussed. In addition, novel insights into tumor genetics, biology and immunology, and the mechanisms underlying metastatic dormancy are discussed. As evident from the numerous studies discussed in this review, the increasing knowledge of this disease and the promising results from testing of novel individualized therapies could offer future perspectives for translating in clinical use.

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The Cancer Genome Atlas Project: An Integrated Molecular View of Uveal Melanoma

Cited by 81 publications

References 25 publications

Uveal Melanoma-Derived Extracellular Vesicles Display Transforming Potential and Carry Protein Cargo Involved in Metastatic Niche Preparation

Uveal Melanoma-Derived Extracellular Vesicles Display Transforming Potential and Carry Protein Cargo Involved in Metastatic Niche Preparation

Alternative Splicing Events as Indicators for the Prognosis of Uveal Melanoma

Molecular Insights and Emerging Strategies for Treatment of Metastatic Uveal Melanoma

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