1,724,542 research outputs found
Alton (A) 4348
No full textA photograph print showing Alton (A) 4348, 2-8-2, on mixed freight, near Independence, MO
Abstract 4348: Methylation analysis of uveal melanoma reveals definitive patterns in tumors harboring BAP1 mutations
No full textAbstract
Introduction: Uveal melanoma (UM) is the most common primary intraocular malignancy and can be classified by gene expression profiling into two distinct molecular classes that correspond to metastatic risk: Class 1 (low risk) and Class 2 (high risk). The less aggressive Class 1 UMs express a more differentiated phenotype and exhibit numerous characteristics of normal uveal melanocytes, while the metastasizing Class 2 UMs display loss of melanocytic differentiation and have acquired a primitive, stem-like phenotype. The majority of Class 2 UMs harbor loss of chromosome 3 in addition to inactivating mutations of the tumor suppressor BAP1, which also catalyzes ubiquitin removal from histone H2A and modulates gene expression. Histone modifications have been shown to be associated with DNA methylation and this study investigates the global methylation and gene expression changes in BAP1 mutant tumors.
Methods: RNA-Sequencing data and Illumina Human Methyl 450K BeadChip Array data obtained from 92 primary uveal melanoma tumors was analyzed using optimized pipelines.
Results: This analysis revealed that the more aggressive Class 2 tumors exhibit a distinct pattern of hypermethylation and silencing of developmental genes involved in neural crest migration and differentiation. Chromosomal regions that were significantly enriched for hypermethylated genes with decreased gene expression in Class 2 tumors included chromosome 3p14-26, 3q12-29 and 8p12-22, whereas the only significantly enriched region for genes that were hypomethylated with increased gene expression in Class 2 tumors was chromosome 8q22-24. Additionally, BAP1 itself was differentially hypermethylated in Class 2 UMs, suggesting that it may regulate its own transcription.
Conclusions: Class 2 UMs harboring BAP1 mutations displayed distinct regions of differential hypermethylation in comparison to Class 1 UMs. In these tumors, the most significantly hypermethylated regions occurred on chromosome 3 and in regions that were enriched for genes encoding neural crest guidance cue proteins that regulate homing, migration and invasion. These findings suggest that BAP1 mutations are associated with marked reorganization of the DNA methylome, providing new insights into the pathophysiology of UM and suggesting that methylation may serve as a diagnostic to further stratify metastatic risk. Furthermore, these findings may open new opportunities for targeted therapy of Class 2 UMs.
Citation Format: Michael Durante, Matthew Field, Stefan Kurtenbach, Parker Bussies, Christina Decatur, J. William Harbour. Methylation analysis of uveal melanoma reveals definitive patterns in tumors harboring BAP1 mutations [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 4348. doi:10.1158/1538-7445.AM2017-4348</jats:p
Block Card 4348 Overland Parkway
No full textThis image was produced by the Auditor's Office in Lucas County, Ohio for tax assessment purposes. Associated dates are approximate. Descriptive terms related to this photograph include: Dwelling (Toledo, Ohio) | Cross gabled | Homeville Subdivision (Toledo, Ohio) | Willys Park area (Toledo, Ohio) | West Toledo (Toledo, Ohio) | 4348 Overland Parkway (Toledo, Ohio
Block Card 4348 Parrakeet Avenue
No full textThis image was produced by the Auditor's Office in Lucas County, Ohio for tax assessment purposes. Associated dates are approximate. Descriptive terms related to this photograph include: dwelling | 4348 Parraket Avenue (Toledo, Ohio) | Garrison style | Elmwood Park (Toledo, Ohio) | Willys Park area (Toledo, Ohio) | West Toledo (Toledo, Ohio
Reconstruction of road III/4348 Troubky - Vlkoš
No full textBakalářská práce se zabývá rekonstrukcí silnice III/4348 mezi obcemi Troubky a Vlkoš. Důvodem této rekonstrukce je napravení směrového a výškového řešení stávající trasy. Tím dojde hlavně ke zvýšení bezpečnosti v tomto úseku. Byly zjištěny původní parametry trasy a navrhnuty 2 varianty řešení rekonstrukce.This bachelor thesis deals with the reconstruction of road III/4348 Troubky – Vlkoš. The reason for reconstruction is to repair directional and vertical course of the road. The road will be safer in this part. Original parameters were determined and then 2 options of solution the reconstruction were designed.
Block Card 4348 Birchall Road
No full textThis image was produced by the Auditor's Office in Lucas County, Ohio for tax assessment purposes. Associated dates are approximate. Descriptive terms related to this photograph include: Dwelling (Toledo, Ohio) | Garrison style | Homeville Subdivision (Toledo, Ohio) | Willys Park area (Toledo, Ohio) | West Toledo (Toledo, Ohio) | 4348 Birchall Road (Toledo, Ohio
Legislative Alert: H.R. 4348
Get PDF[Excerpt] On behalf of the AFL-CIO. I write in strong support of H.R. 4348, a bill to extend the surface transportation law until September 30, 2012. Time is running out to reauthorize the massive transportation infrastructure bill, which is currently operating on its ninth extension. Any further delay will render state and local governments unable to plan for the remainder of the construction season, putting tens of thousands of jobs at risk
Reconstruction of road III/4348 Troubky - Vlkoš
No full textThis bachelor thesis deals with the reconstruction of road III/4348 Troubky – Vlkoš. The reason for reconstruction is to repair directional and vertical course of the road. The road will be safer in this part. Original parameters were determined and then 2 options of solution the reconstruction were designed
Linked collectors and determiners for: Revision of the Exechia parva group (Diptera: Mycetophilidae).
No full textNatural history specimen data linked to collectors and determiners held within, "Revision of the Exechia parva group (Diptera: Mycetophilidae)". Claims or attributions were made on Bionomia by volunteer Scribes, <a href="http://bionomia.net/dataset/86edee65-e1c5-4348-a5ef-fcac71dbce74">https://bionomia.net/dataset/86edee65-e1c5-4348-a5ef-fcac71dbce74</a> using specimen data from the dataset aggregated by the Global Biodiversity Information Facility, <a href="https://gbif.org/dataset/86edee65-e1c5-4348-a5ef-fcac71dbce74">https://gbif.org/dataset/86edee65-e1c5-4348-a5ef-fcac71dbce74</a>. Formatted as a Frictionless Data package
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