Genomics

Dataset Information

0

Expression changes in Melanomas pre MAPKi treatment vs. on MAPKi treatment [Y1.7.FPKM.batch1.2]


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.

ORGANISM(S): Mus musculus

PROVIDER: GSE103725 | GEO | 2017/09/13

SECONDARY ACCESSION(S): PRJNA406876

REPOSITORIES: GEO

Similar Datasets

2017-09-05 | GSE75311 | GEO
2017-09-08 | GSE103658 | GEO
2017-09-05 | GSE75299 | GEO
2017-09-08 | GSE103630 | GEO
2017-09-12 | GSE103712 | GEO
2017-09-12 | GSE103711 | GEO
2017-09-12 | GSE103688 | GEO
2017-09-12 | GSE103687 | GEO
2017-09-12 | GSE103713 | GEO
2022-05-31 | GSE199733 | GEO