Transcriptomic analysis of BAP1 negative primary and metastatic uveal melanoma tumors
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE145782 | GEO | 2020/02/26
REPOSITORIES: GEO
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Project description:Transcriptomic analysis of BAP1 negative primary and metastatic uveal melanoma tumors
| PRJNA608679 | ENA
Project description:Uveal melanoma is a highly aggressive cancer with a strong propensity for metastasis, yet little is known about the biological mechanisms underlying this metastatic potential. We recently showed that most metastasizing uveal melanomas, which exhibit a class 2 gene expression profile, contain inactivating mutations in the tumor suppressor BAP1. The aim of this study was to investigate the role of BAP1 in uveal melanoma progression. To that end, uveal melanoma cells were studied following stable shRNA-mediated depletion of BAP1. RNA was isolated from three independent uveal melanoma cell lines each stably depleted using shRNA for either BAP1 or the control gene GFP. Two biological replicates were performed for each cell line.
2013-09-06 | E-GEOD-48863 | biostudies-arrayexpress
Project description:OCM-1A uveal melanoma cells were infected with lentivirus carrying shRNA expression constructs specific for BAP1 or GFP (control), and placed under selection for 6 days. RNA-seq was performed.
2018-10-15 | GSE110193 | GEO
Project description:Uveal melanoma is an aggressive cancer that metastasizes to the liver in about half of patients, being at that time almost always fatal. Identification of patients at high risk of metastases may provide indication for a frequent follow-up for early detection of metastases and treatment. The analysis of the gene expression profiling of primary human uveal melanomas showed high expression of SDCBP (encoding for syndecan-binding protein-1 or syntenin-1), which appeared higher in patients with recurrence, whereas expression of syndecans was lower and unrelated to progression. Moreover, we found that high expression of SDCBP gene was related to metastatic progression in two additional independent dataset of uveal melanoma patients. More importantly, immunohistochemistry showed that high expression of syntenin-1 protein in primary tumours was significantly related to metastatic recurrence in our cohort of patients. Syntenin-1 expression was confirmed by RT-PCR, immunofluorescence and immunohistochemistry in cultured uveal melanoma cells or primary tumours. A pseudo-metastatic model of uveal melanoma to the liver was developed in NOD/SCID/IL2R null mice and the study of syntenin-1 expression in primary and metastatic lesions revealed higher syntenin-1 expression in metastases. The inhibition of SDCBP expression by siRNA impaired the ability of uveal melanoma cells to migrate in a woundâhealing assay. These results suggest that SDCBP is involved in uveal melanoma progression and that it represents a candidate molecular marker of metastases and a potential therapeutic target. Gene expression profiles of 29 unique samples from uveal melanoma patients were measured.
2012-04-17 | E-GEOD-27831 | biostudies-arrayexpress
Project description:Uveal melanoma cells are resistant to EZH2 inhibition regardless of BAP1 status
2016-06-06 | GSE79905 | GEO
Project description:Uveal melanoma is a highly aggressive cancer with a strong propensity for metastasis, yet little is known about the biological mechanisms underlying this metastatic potential. We recently showed that most metastasizing uveal melanomas, which exhibit a class 2 gene expression profile, contain inactivating mutations in the tumor suppressor BAP1. The aim of this study was to investigate the role of BAP1 in uveal melanoma progression. To that end, uveal melanoma cells were studied following stable shRNA-mediated depletion of BAP1.
2013-09-06 | GSE48863 | GEO
Project description:Metastatic uveal melanoma generally responds poorly to immunotherapy. The aim here was to sequence tumor-infiltrating lymphocytes from uveal melanoma metastases to study their phenotypes and T-cell receptor (TCR) clonotypes. We performed paired single-cell transcriptome and TCR sequencing using the 10x Genomics platform of IL2-expanded tumor-infiltrating lymphocytes from 7 liver and 1 subcutaneous metastasis.
2020-03-16 | E-MTAB-8846 | biostudies-arrayexpress
Project description:Uveal melanoma is an aggressive cancer that metastasizes to the liver in about half of patients, being at that time almost always fatal. Identification of patients at high risk of metastases may provide indication for a frequent follow-up for early detection of metastases and treatment. The analysis of the gene expression profiling of primary human uveal melanomas showed high expression of SDCBP (encoding for syndecan-binding protein-1 or syntenin-1), which appeared higher in patients with recurrence, whereas expression of syndecans was lower and unrelated to progression. Moreover, we found that high expression of SDCBP gene was related to metastatic progression in two additional independent dataset of uveal melanoma patients. More importantly, immunohistochemistry showed that high expression of syntenin-1 protein in primary tumours was significantly related to metastatic recurrence in our cohort of patients. Syntenin-1 expression was confirmed by RT-PCR, immunofluorescence and immunohistochemistry in cultured uveal melanoma cells or primary tumours. A pseudo-metastatic model of uveal melanoma to the liver was developed in NOD/SCID/IL2R null mice and the study of syntenin-1 expression in primary and metastatic lesions revealed higher syntenin-1 expression in metastases. The inhibition of SDCBP expression by siRNA impaired the ability of uveal melanoma cells to migrate in a wound–healing assay. These results suggest that SDCBP is involved in uveal melanoma progression and that it represents a candidate molecular marker of metastases and a potential therapeutic target.
2012-04-18 | GSE27831 | GEO
Project description:Genome wide DNA methylation profiling of primary uveal melanoma cells, normal uveal melanocytes, neural crest stem cells, embryonic stem cells and uveal melanoma cell lines. The Illumina Infinium 27k Human DNA methylation Beadchip Rev B was used to obtain DNA methylation profiles across approximately 27,000 CpGs in the samples. Samples included 58 primary UM, 3 NUM and NCSC controls and 2 cell lines. Bisulphite converted DNA from the 63 samples were hybridised to the Illumina Infinium 27k Human Methylation Beadchip Rev B
2013-02-14 | E-GEOD-44296 | biostudies-arrayexpress
Project description:Uveal melanoma (UM) is a rare form of melanoma with a genetics and immunology that is different from skin melanoma. Previous studies have identified genetic driver events of early stage disease when the tumor is confined to the eye. In this study, we have characterized genomic events in UM metastases using whole-genome and RNA sequencing from thirty-two and twenty-eight patients, respectively, and profiled individual tumor infiltrating lymphocytes in a number of the metastases. We find that 91% of the patients have metastases carrying inactivating events in the tumor suppressor BAP1 and this coincided with somatic alterations in GNAQ, GNA11, CYSLTR2, PLCB4, SF3B1 and/or CDKN2A. Mutational signature analysis revealed a rare subset of tumors with prominent signs of UV damage, associated with outlier mutational burden. We study copy number variations (CNV) and find overrepresented events, some of which were not altered in matched primary eye tumors. A focused siRNA screen identified functionally significant genes of some of the segments recurrently gained. We reintroduced a functional copy of BAP1 into a patient-derived BAP1 deficient tumor cell line and found broad transcriptomic changes of genes associated with subtype distinction and prognosis in primary UM. Lastly, our analysis of the immune microenvironments of metastases revealed a presence of tumor-reactive T cells. However, a large fraction expressed the immune checkpoint receptors such as TIM-3, TIGIT and LAG3. These results provide an updated view of genomic events represented in metastatic UM and immune interactions in advanced lesions.
2020-03-18 | PXD017743 | Pride