Genomics

Dataset Information

42

Expression changes in YUMM1.7 melanoma with/without PD-L2 overexpression under BRAFi treatment in NSG mice [Y1.7.FPKM.batch4]


ABSTRACT: 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

INSTRUMENT(S): Illumina HiSeq 3000 (Mus musculus)

SUBMITTER: Willy Hugo  

PROVIDER: GSE103713 | GEO | 2017-09-12

SECONDARY ACCESSION(S): PRJNA406730

REPOSITORIES: GEO

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Treatment of advanced <i>BRAF</i><sup>V600</sup>-mutant melanoma using a BRAF inhibitor or its combination with a MEK inhibitor typically elicits partial responses. We compared the transcriptomes of patient-derived tumors regressing on MAPK inhibitor (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 tr  ...[more]

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