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Title: Expression changes in pre MAPKi treatment and post MAPKi resistance Melanomas      
dateReleased:
09-15-2015
description:
Melanoma resistance to MAPK- or T cell checkpoint-targeted therapies represents a major clinical challenge, and treatment failures of MAPK-targeted therapies due to acquired resistance often require salvage immunotherapies. We show that genomic analysis of acquired resistance to MAPK inhibitors revealed key driver genes but failedto adequately account for clinical resistance. From a large-scale comparative analysis of temporal transcriptomes from patient-matched tumor biopsies, we discovered highly recurrent differential expression and signature outputs of c-MET, LEF1 and YAP1 as drivers of acquired MAPK inhibitor resistance. Moreover, integration of gene- and signature-based transcriptomic analysis revealed profound CD8 T cell deficiency detected in half of resistant melanomas in association with downregulation of dendritic cells and antigen presentation. We also propose a major methylomic basis to transcriptomic evolution under MAPK inhibitor selection. Thus, this database provides a rich informational resource, and the current landscape represents a benchmark to understanding melanoma therapeutic resistance. Melanoma biopsies pre and post MAPKi treatment were sent for transcriptomic analysis using Affymetrix HuGene 2.1 microarray
privacy:
not applicable
aggregation:
instance of dataset
ID:
E-GEOD-65184
refinement:
raw
alternateIdentifiers:
65184
keywords:
functional genomics
dateModified:
09-20-2015
availability:
available
types:
gene expression
name:
Homo sapiens
ID:
A-GEOD-17692
name:
[HuGene-2_1-st] Affymetrix Human Gene 2.1 ST Array [transcript (gene) version]
accessURL: https://www.ebi.ac.uk/arrayexpress/files/E-GEOD-65184/E-GEOD-65184.raw.1.zip
storedIn:
ArrayExpress
qualifier:
gzip compressed
format:
TXT
accessType:
download
authentication:
none
authorization:
none
accessURL: https://www.ebi.ac.uk/arrayexpress/files/E-GEOD-65184/E-GEOD-65184.processed.1.zip
storedIn:
ArrayExpress
qualifier:
gzip compressed
format:
TXT
accessType:
download
authentication:
none
authorization:
none
accessURL: https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE65184
storedIn:
Gene Expression Omnibus
qualifier:
not compressed
format:
HTML
accessType:
landing page
primary:
true
authentication:
none
authorization:
none
abbreviation:
EBI
homePage: http://www.ebi.ac.uk/
ID:
SCR:004727
name:
European Bioinformatics Institute
homePage: https://www.ebi.ac.uk/arrayexpress/
ID:
SCR:002964
name:
ArrayExpress

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