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Series GSE103713 Query DataSets for GSE103713
Status Public on Sep 12, 2017
Title Expression changes in YUMM1.7 melanoma with/without PD-L2 overexpression under BRAFi treatment in NSG mice [Y1.7.FPKM.batch4]
Organism Mus musculus
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 YUMM1.7 melanoma tumors in NOD/SCID mice with and without PD-L2 expression in baseline (vehicle treated) and BRAFi resistance were sent for transcriptomic analysis by single end 1x50bp HiSeq 3000 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
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
 
Platforms (1)
GPL21493 Illumina HiSeq 3000 (Mus musculus)
Samples (12)
GSM2779596 Y1.7-NSG-Ctrl-DMSO-1
GSM2779597 Y1.7-NSG-Ctrl-DMSO-2
GSM2779598 Y1.7-NSG-Ctrl-DMSO-3
This SubSeries is part of SuperSeries:
GSE75313 Expression changes in Melanomas pre MAPKi treatment vs. on MAPKi treatment
Relations
BioProject PRJNA406730
SRA SRP117274

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
GSE103713_Y1.7.FPKM.batch4.xlsx 2.8 Mb (ftp)(http) XLSX
SRA Run SelectorHelp
Raw data are available in SRA
Processed data are available on Series record

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