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Series GSE103687 Query DataSets for GSE103687
Status Public on Sep 12, 2017
Title Expression changes in melanoma cell lines under BRAFi treatment timepoints [RNA-Seq.CellLine.batch4]
Organism Homo sapiens
Experiment type Expression profiling by high throughput sequencing
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.
Overall design Paired melanoma cell lines before treatment and during BRAFi treatment were sent for transcriptomic analysis by single end 1x50bp RNAseq analysis
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
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)
GPL21290 Illumina HiSeq 3000 (Homo sapiens)
Samples (8)
GSM2779261 M397 P2
GSM2779262 M397 BRAFi2D
GSM2779263 M397 DTP
This SubSeries is part of SuperSeries:
GSE75313 Expression changes in Melanomas pre MAPKi treatment vs. on MAPKi treatment
BioProject PRJNA404059
SRA SRP117244

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Supplementary file Size Download File type/resource
GSE103687_CellLine.FPKM.batch4.xlsx 2.2 Mb (ftp)(http) XLSX
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Processed data are available on Series record

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