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BAP1 loss triggers DNA methylomic repatterning in highly aggressive Class 2 uveal melanomas [RNA-Seq]

ABSTRACT: The strong association between BAP1 mutations and highly aggressive Class 2 uveal melanoma (UM) suggests that epigenetic alterations may play a significant role in tumor progression. Thus, we characterized the impact of BAP1 loss on the DNA methylome in UM.

ORGANISM(S): Homo sapiens

PROVIDER: GSE130356 | GEO | 2020/04/04

REPOSITORIES: GEO

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BAP1 loss triggers DNA methylomic repatterning in highly aggressive Class 2 uveal melanomas [MethylationEPIC]

Project description:The strong association between BAP1 mutations and highly aggressive Class 2 uveal melanoma (UM) suggests that epigenetic alterations may play a significant role in tumor progression. Thus, we characterized the impact of BAP1 loss on methylomic repatterning in UM.

2020-04-04 | GSE130295 | GEO

BAP1 loss triggers DNA methylomic repatterning in highly aggressive Class 2 uveal melanomas [BeadChip 450K]

2020-04-04 | GSE130354 | GEO

BAP1 Loss Is Associated with DNA Methylomic Repatterning in Highly Aggressive Class 2 Uveal Melanomas.

Project description:PurposeThe strong association between BAP1 mutations and metastasizing Class 2 uveal melanoma (UM) suggests that epigenetic alterations may play a significant role in tumor progression. Thus, we characterized the impact of BAP1 loss on the DNA methylome in UM.Experimental Design: Global DNA methylation was analyzed in 47 Class 1 and 45 Class 2 primary UMs and in UM cells engineered to inducibly deplete BAP1. RNA-Seq was analyzed in 80 UM samples and engineered UM cells.ResultsHypermethylation on chromosome 3 correlated with downregulated gene expression at several loci, including 3p21, where BAP1 is located. Gene set analysis of hypermethylated and downregulated genes identified axon guidance and melanogenesis as deregulated pathways, with several of these genes located on chromosome 3. A novel hypermethylated site within the BAP1 locus was found in all Class 2 tumors, suggesting that BAP1 itself is epigenetically regulated. Highly differentially methylated probes were orthogonally validated using bisulfite sequencing, and they successfully distinguished Class 1 and Class 2 tumors in 100% of cases. In functional validation experiments, BAP1 knockdown in UM cells induced methylomic repatterning similar to UM tumors, enriched for genes involved in axon guidance, melanogenesis, and development.ConclusionsThis study, coupled with previous work, suggests that the initial event in the divergence of Class 2 UM from Class 1 UM is loss of one copy of chromosome 3, followed by mutation of BAP1 on the remaining copy of chromosome 3, leading to the methylomic repatterning profile characteristic of Class 2 UMs.

| S-EPMC6744995 | biostudies-literature

BAP1 loss triggers DNA methylomic repatterning in highly aggressive Class 2 uveal melanomas

Project description:BAP1 loss triggers DNA methylomic repatterning in highly aggressive Class 2 uveal melanomas

| PRJNA539867 | ENA

BAP1 loss triggers DNA methylomic repatterning in highly aggressive Class 2 uveal melanomas

Project description:This SuperSeries is composed of the SubSeries listed below.

2020-04-04 | GSE130357 | GEO

BAP1 loss triggers DNA methylomic repatterning in highly aggressive Class 2 uveal melanomas [MethylationEPIC]

Project description:BAP1 loss triggers DNA methylomic repatterning in highly aggressive Class 2 uveal melanomas [MethylationEPIC]

| PRJNA539865 | ENA

BAP1 loss triggers DNA methylomic repatterning in highly aggressive Class 2 uveal melanomas [BeadChip 450K]

Project description:BAP1 loss triggers DNA methylomic repatterning in highly aggressive Class 2 uveal melanomas [BeadChip 450K]

| PRJNA539870 | ENA

BAP1 loss triggers DNA methylomic repatterning in highly aggressive Class 2 uveal melanomas [RNA-Seq]

Project description:BAP1 loss triggers DNA methylomic repatterning in highly aggressive Class 2 uveal melanomas [RNA-Seq]

| PRJNA539871 | ENA

RNA-seq analysis of BAP1 mutant and wild-type uveal melanoma cell lines

Project description:Inactivating mutations of BAP1 are associated with an increased risk of developing metastasis in uveal melanoma (UM), but the roles of BAP1 in UM progression is unclear. To characterize BAP1’s functions in UM, we performed RNA sequencing on BAP1 wild-type and mutant UM cell lines. Differential analysis revealed that BAP1 loss is associated with an upregulated gene expression profile of multiple cell adhesion molecules (CAMs), including E-cadherin (CDH1), cell adhesion molecule 1 (CADM1), and syndecan-2 (SDC2).

2022-04-25 | GSE181194 | GEO

Gene expression changes resulting from the stable loss of BAP1 in uveal melanoma cell lines

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

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