Transcriptomics,Genomics

Dataset Information

271

MRNA expressions in pre-treatment melanomas undergoing anti-PD-1 checkpoint inhibition therapy


ABSTRACT: PD-1 immune checkpoint blockade provides significant clinical benefits for cancer patients. However, factors influencing innate sensitivity remain incompletely catalogued. We analyzed the somatic mutanomes and transcriptomes of pretreatment melanoma biopsies. Mutations in cell adhesion genes and the DNA repair gene BRCA2 were enriched in responding tumors, and a high mutational load associated with improved survival. Innately resistant tumors displayed frequent transcriptomic up-expression of genes that enriched for mesenchymal transition, cell adhesion, ECM organization, wound-healing and angiogenesis. The transcriptomes of innate resistance also enriched for signatures indicating up-regulation of these processes. Notably, MAPK-targeted therapy (MAPKi) induced similar signatures in melanoma, suggesting that a form of MAPKi resistance mediates cross-resistance to anti-PD-1 therapy. Co-enrichment of IPRIM (Innate anti-PD-1 Resistance Induced by MAPKi) signatures defined a transcriptomic subset across advanced cancers, suggesting that attenuating processes underlying these signatures may augment anti-PD1 responses. Thus, multi-factorial determinants influence anti-PD-1 patterns in melanoma. Overall design: Melanoma biopsies pre-anti-PD-1 therapy were sent for transcriptomic analysis by paired-end RNAseq analysis to find the correlates of response vs. non-response to the therapy

INSTRUMENT(S): Illumina HiSeq 2000 (Homo sapiens)

SUBMITTER: Willy Hugo  

PROVIDER: GSE78220 | GEO | 2016-03-18

SECONDARY ACCESSION(S): PRJNA312948

REPOSITORIES: GEO

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Publications


PD-1 immune checkpoint blockade provides significant clinical benefits for melanoma patients. We analyzed the somatic mutanomes and transcriptomes of pretreatment melanoma biopsies to identify factors that may influence innate sensitivity or resistance to anti-PD-1 therapy. We find that overall high mutational loads associate with improved survival, and tumors from responding patients are enriched for mutations in the DNA repair gene BRCA2. Innately resistant tumors display a transcriptional sig  ...[more]

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