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Series GSE65183 Query DataSets for GSE65183
Status Public on Sep 15, 2015
Title Methylation changes in pre MAPKi treatment and post MAPKi resistance Melanomas
Organism Homo sapiens
Experiment type Methylation profiling by genome tiling array
Summary 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.
Overall design Melanoma biopsies pre and post MAPKi treatment were sent for DNA methylation analysis using Illumina Human Methylation 450K bead chips
Contributor(s) Hugo W, Shi H, Sun L, Piva M, Song C, Kong X, Moriceau G, Hong A, Dahlman KB, Johnson DB, Sosman JA, Ribas A, Lo RS
Citation(s) 26359985
Submission date Jan 22, 2015
Last update date Mar 22, 2019
Contact name Willy Hugo
Organization name UCLA
Department Medicine
Street address 10833 Le Conte Ave, 52-121 CHS, Division of Dermatology
City Los Angeles
State/province California
ZIP/Postal code 90095
Country USA
Platforms (1)
GPL13534 Illumina HumanMethylation450 BeadChip (HumanMethylation450_15017482)
Samples (144)
GSM1588704 Pt1-baseline-1
GSM1588705 Pt1-baseline-2
GSM1588706 Pt1-DP1-1
This SubSeries is part of SuperSeries:
GSE65186 Non-genomic and Immune Evolution in Melanoma with Acquired MAPKi Resistance
BioProject PRJNA273361

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE65183_RAW.tar 1.3 Gb (http)(custom) TAR (of IDAT)
Processed data included within Sample table

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