FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W4311763505> ?p ?o ?g. }

• W4311763505 endingPage "853.e6" @default.
• W4311763505 startingPage "842" @default.
• W4311763505 abstract "Although tremendous progress has been made in targeted and immune-based treatments for advanced melanoma, there remains a substantial therapeutic failure rate. For patients with BRAF(V600)-mutant melanomas, resistance to BRAF inhibitors remains a significant survival hurdle. Although multiple compensatory mechanisms to bypass BRAF blockade have been discovered, the epigenetic patterns are still poorly characterized. In this report, we generated eight matched pairs of vemurafenib-sensitive/-resistant melanoma lines and subjected these to concurrent RNA-sequencing and H3K27ac chromatin immunoprecipitation sequencing analysis. Globally, we identified two classes of epigenetic profiles that correlate with resistance. Class 1 resistance involves fewer RNA expression alterations accompanied by fewer enhancer mark changes with H3K27ac. Class 2 resistance shows widespread alterations in transcription and enhancer profiles, which converge on epithelial‒mesenchymal transition and hypoxia-related pathways. We also observed significant and dynamic changes in superenhancers that underpin these transcriptomic patterns. We subsequently verified the two-class structure in pre-BRAF inhibitors and postrelapse human melanoma specimens. Our findings reveal a broad and underappreciated spectrum of epigenetic plasticity during acquired BRAF inhibitor resistance. Although tremendous progress has been made in targeted and immune-based treatments for advanced melanoma, there remains a substantial therapeutic failure rate. For patients with BRAF(V600)-mutant melanomas, resistance to BRAF inhibitors remains a significant survival hurdle. Although multiple compensatory mechanisms to bypass BRAF blockade have been discovered, the epigenetic patterns are still poorly characterized. In this report, we generated eight matched pairs of vemurafenib-sensitive/-resistant melanoma lines and subjected these to concurrent RNA-sequencing and H3K27ac chromatin immunoprecipitation sequencing analysis. Globally, we identified two classes of epigenetic profiles that correlate with resistance. Class 1 resistance involves fewer RNA expression alterations accompanied by fewer enhancer mark changes with H3K27ac. Class 2 resistance shows widespread alterations in transcription and enhancer profiles, which converge on epithelial‒mesenchymal transition and hypoxia-related pathways. We also observed significant and dynamic changes in superenhancers that underpin these transcriptomic patterns. We subsequently verified the two-class structure in pre-BRAF inhibitors and postrelapse human melanoma specimens. Our findings reveal a broad and underappreciated spectrum of epigenetic plasticity during acquired BRAF inhibitor resistance." @default.
• W4311763505 created "2022-12-28" @default.
• W4311763505 creator A5017303827 @default.
• W4311763505 creator A5026137065 @default.
• W4311763505 creator A5030384915 @default.
• W4311763505 creator A5084619384 @default.
• W4311763505 date "2023-05-01" @default.
• W4311763505 modified "2023-10-18" @default.
• W4311763505 title "Divergent BRAF Inhibitor Resistance Mechanisms Revealed through Epigenetic Mapping" @default.
• W4311763505 cites W1490559159 @default.
• W4311763505 cites W1896068186 @default.
• W4311763505 cites W1971578941 @default.
• W4311763505 cites W1982393730 @default.
• W4311763505 cites W1985928174 @default.
• W4311763505 cites W2004966039 @default.
• W4311763505 cites W2009642188 @default.
• W4311763505 cites W2025130458 @default.
• W4311763505 cites W2038264590 @default.
• W4311763505 cites W2043058822 @default.
• W4311763505 cites W2045449074 @default.
• W4311763505 cites W2060484997 @default.
• W4311763505 cites W2060938351 @default.
• W4311763505 cites W2075240818 @default.
• W4311763505 cites W2080626878 @default.
• W4311763505 cites W2100969832 @default.
• W4311763505 cites W2103287271 @default.
• W4311763505 cites W2106423189 @default.
• W4311763505 cites W2116978375 @default.
• W4311763505 cites W2159220884 @default.
• W4311763505 cites W2164992866 @default.
• W4311763505 cites W2176310149 @default.
• W4311763505 cites W2186855780 @default.
• W4311763505 cites W2226721679 @default.
• W4311763505 cites W2335844855 @default.
• W4311763505 cites W2516391536 @default.
• W4311763505 cites W2608984150 @default.
• W4311763505 cites W2616008845 @default.
• W4311763505 cites W2753512521 @default.
• W4311763505 cites W2754854521 @default.
• W4311763505 cites W2770829476 @default.
• W4311763505 cites W2787863806 @default.
• W4311763505 cites W2797189509 @default.
• W4311763505 cites W2811032414 @default.
• W4311763505 cites W2967888979 @default.
• W4311763505 cites W2999417355 @default.
• W4311763505 cites W3006719485 @default.
• W4311763505 cites W3044823707 @default.
• W4311763505 cites W3047437275 @default.
• W4311763505 cites W3162889843 @default.
• W4311763505 doi "https://doi.org/10.1016/j.jid.2022.03.039" @default.
• W4311763505 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/36529262" @default.
• W4311763505 hasPublicationYear "2023" @default.
• W4311763505 type Work @default.
• W4311763505 citedByCount "0" @default.
• W4311763505 crossrefType "journal-article" @default.
• W4311763505 hasAuthorship W4311763505A5017303827 @default.
• W4311763505 hasAuthorship W4311763505A5026137065 @default.
• W4311763505 hasAuthorship W4311763505A5030384915 @default.
• W4311763505 hasAuthorship W4311763505A5084619384 @default.
• W4311763505 hasConcept C104317684 @default.
• W4311763505 hasConcept C2776131300 @default.
• W4311763505 hasConcept C2777658100 @default.
• W4311763505 hasConcept C2777701055 @default.
• W4311763505 hasConcept C2780851360 @default.
• W4311763505 hasConcept C2994587330 @default.
• W4311763505 hasConcept C41091548 @default.
• W4311763505 hasConcept C502942594 @default.
• W4311763505 hasConcept C54355233 @default.
• W4311763505 hasConcept C83640560 @default.
• W4311763505 hasConcept C86803240 @default.
• W4311763505 hasConcept C8891405 @default.
• W4311763505 hasConceptScore W4311763505C104317684 @default.
• W4311763505 hasConceptScore W4311763505C2776131300 @default.
• W4311763505 hasConceptScore W4311763505C2777658100 @default.
• W4311763505 hasConceptScore W4311763505C2777701055 @default.
• W4311763505 hasConceptScore W4311763505C2780851360 @default.
• W4311763505 hasConceptScore W4311763505C2994587330 @default.
• W4311763505 hasConceptScore W4311763505C41091548 @default.
• W4311763505 hasConceptScore W4311763505C502942594 @default.
• W4311763505 hasConceptScore W4311763505C54355233 @default.
• W4311763505 hasConceptScore W4311763505C83640560 @default.
• W4311763505 hasConceptScore W4311763505C86803240 @default.
• W4311763505 hasConceptScore W4311763505C8891405 @default.
• W4311763505 hasFunder F4320308296 @default.
• W4311763505 hasFunder F4320308349 @default.
• W4311763505 hasIssue "5" @default.
• W4311763505 hasLocation W43117635051 @default.
• W4311763505 hasLocation W43117635052 @default.
• W4311763505 hasOpenAccess W4311763505 @default.
• W4311763505 hasPrimaryLocation W43117635051 @default.
• W4311763505 hasRelatedWork W1988432435 @default.
• W4311763505 hasRelatedWork W2404580886 @default.
• W4311763505 hasRelatedWork W2528389484 @default.
• W4311763505 hasRelatedWork W2796527216 @default.
• W4311763505 hasRelatedWork W2912365614 @default.
• W4311763505 hasRelatedWork W2922270413 @default.
• W4311763505 hasRelatedWork W3092419705 @default.
• W4311763505 hasRelatedWork W4234665826 @default.

• next