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| Status |
Public on Sep 12, 2017 |
| Title |
Expression changes in MAPKi resistant M229 melanoma lines co-cultured with PD-1 overexpressing HEK293T cells [CellLine.FPKM.batch5] |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Treatment of advanced V600BRAF mutant melanoma using a BRAF inhibitor (BRAFi) or its combination with a MEKi typically elicits partial responses. We compared the transcriptomes of patient-derived tumors regressing on MAPKi therapy against MAPKi-induced temporal transcriptomic states in human melanoma cell lines or murine melanoma in immune-competent mice. Despite heterogeneous dynamics of clinical tumor regression, residual tumors displayed highly recurrent transcriptomic alterations and enriched processes, which were also observed in MAPKi-selected cell lines (implying tumor cell-intrinsic reprogramming) or in bulk mouse tumors (and the CD45-negative or -positive fractions,, implying tumor cell-intrinsic or stromal/immune alterations, respectively). Tumor cell-intrinsic reprogramming attenuated MAPK-dependency, while enhancing mesenchymal, angiogenic and IFN-inflammatory features and growth/survival dependence on multi-RTKs and PD-L2. In the immune compartment, PD-L2 upregulation in CD11c+ immunocytes drove the loss of T-cell inflammation and promoted BRAFi resistance. Thus, residual melanoma early on MAPKi therapy already displays potentially exploitable adaptive transcriptomic, epigenomic, immune-regulomic alterations.
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| Overall design |
M229 SDR and DDR lines cocultured with PD-1/GFP-control expressing HEK293T cells and with/without staurosporine treatment were sorted to yield purified melanoma population which were sent for transcriptomic analysis by single end 1x50bp HiSeq3000 RNAseq analysis
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| Contributor(s) |
Song C, Piva M, Sun L, Hong A, Moriceau G, Kong X, Zhang H, Lomeli S, Qian J, Yu CC, Damoiseaux R, Kelley MC, Dahlman KB, Scumpia PO, Sosman JA, Johnson DB, Ribas A, Hugo W, Lo RS |
| Citation(s) |
28864476 |
| Submission date |
Sep 11, 2017 |
| Last update date |
May 15, 2019 |
| Contact name |
Willy Hugo |
| E-mail(s) |
hwilly@mednet.ucla.edu
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| Organization name |
UCLA
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| Department |
Medicine
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| Street address |
10833 Le Conte Ave, 52-121 CHS, Division of Dermatology
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| City |
Los Angeles |
| State/province |
California |
| ZIP/Postal code |
90095 |
| Country |
USA |
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| Platforms (1) |
| GPL21290 |
Illumina HiSeq 3000 (Homo sapiens) |
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| Samples (16)
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| This SubSeries is part of SuperSeries: |
| GSE75313 |
Expression changes in Melanomas pre MAPKi treatment vs. on MAPKi treatment |
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| Relations |
| BioProject |
PRJNA406732 |
| SRA |
SRP117273 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE103711_M229.SDR.DDR.coCulture.xlsx |
3.9 Mb |
(ftp)(http) |
XLSX |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data are available on Series record |
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