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Series GSE65185 Query DataSets for GSE65185
Status Public on Sep 15, 2015
Title RNAseq changes in pre MAPKi treatment and post MAPKi resistance Melanomas
Organism Homo sapiens
Experiment type Expression profiling by high throughput sequencing
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 RNAseq analysis
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 May 15, 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)
GPL11154 Illumina HiSeq 2000 (Homo sapiens)
Samples (70)
GSM1588852 Pt1-baseline
GSM1588853 Pt1-DP1
GSM1588854 Pt2-baseline
This SubSeries is part of SuperSeries:
GSE65186 Non-genomic and Immune Evolution in Melanoma with Acquired MAPKi Resistance
BioProject PRJNA273359
SRA SRP052740

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Supplementary file Size Download File type/resource
GSE65185_CuffnormFPKM.txt.gz 5.5 Mb (ftp)(http) TXT
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Raw data are available in SRA
Processed data are available on Series record

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