{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Giricz O"],"funding":["Pershing Square Sohn Cancer Research Alliance and Department of Defense","NCI","NCI NIH HHS","NIH","NIH HHS"],"pagination":["120422"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC6124424"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["3(14)"],"pubmed_abstract":["Resistance to current therapies still impacts a significant number of melanoma patients and can be regulated by epigenetic alterations. Analysis of global cytosine methylation in a cohort of primary melanomas revealed a pattern of early demethylation associated with overexpression of oncogenic transcripts. Loss of methylation and associated overexpression of the CSF 1 receptor (CSF1R) was seen in a majority of tumors and was driven by an alternative, endogenous viral promoter in a subset of samples. CSF1R was particularly elevated in melanomas with BRAF and other MAPK activating mutations. Furthermore, rebound ERK activation after BRAF inhibition was associated with RUNX1-mediated further upregulation of CSF-1R and its ligand IL-34. Importantly, increased CSF-1R and IL-34 overexpression we"],"journal":["JCI insight"],"pubmed_title":["The RUNX1/IL-34/CSF-1R axis is an autocrinally regulated modulator of resistance to BRAF-V600E inhibition in melanoma."],"pmcid":["PMC6124424"],"funding_grant_id":["P30 CA013330","S10 OD019961","W81XWH-14-1-0230","SIG 1S10OD019961-01","K12 CA090625","P30CA013330"],"pubmed_authors":["Matusow B","Vardabasso C","Habets G","Shellooe R","West BL","Bhagat TD","Burton E","Zhang C","Mo Y","Yu Y","Bernstein E","Cotto-Rios XM","Tsai J","Gavathiotis E","Dahlman KB","Fields GB","Pradhan K","Polishchuk V","Johnson DB","Greally JM","Nguyen H","Bollag G","Stanley ER","Bartenstein M","Kenny PA","Sosman JA","Verma AK","Giricz O"],"additional_accession":[]},"is_claimable":false,"name":"The RUNX1/IL-34/CSF-1R axis is an autocrinally regulated modulator of resistance to BRAF-V600E inhibition in melanoma.","description":"Resistance to current therapies still impacts a significant number of melanoma patients and can be regulated by epigenetic alterations. Analysis of global cytosine methylation in a cohort of primary melanomas revealed a pattern of early demethylation associated with overexpression of oncogenic transcripts. Loss of methylation and associated overexpression of the CSF 1 receptor (CSF1R) was seen in a majority of tumors and was driven by an alternative, endogenous viral promoter in a subset of samples. CSF1R was particularly elevated in melanomas with BRAF and other MAPK activating mutations. Furthermore, rebound ERK activation after BRAF inhibition was associated with RUNX1-mediated further upregulation of CSF-1R and its ligand IL-34. Importantly, increased CSF-1R and IL-34 overexpression we","dates":{"release":"2018-01-01T00:00:00Z","publication":"2018 Jul","modification":"2026-04-29T02:57:32.173Z","creation":"2019-03-26T23:54:58Z"},"accession":"S-EPMC6124424","cross_references":{"pubmed":["30046005"],"doi":["10.1172/jci.insight.120422"]}}