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| 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.
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| Overall design |
Melanoma biopsies pre and post MAPKi treatment were sent for DNA methylation analysis using Illumina Human Methylation 450K bead chips
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| 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 |
| E-mail(s) |
hwilly@mednet.ucla.edu
|
| 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 |
| |
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| Platforms (1) |
| GPL13534 |
Illumina HumanMethylation450 BeadChip (HumanMethylation450_15017482) |
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| Samples (144)
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| This SubSeries is part of SuperSeries: |
| GSE65186 |
Non-genomic and Immune Evolution in Melanoma with Acquired MAPKi Resistance |
|
| Relations |
| BioProject |
PRJNA273361 |
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