GEO Logo
   NCBI > GEO > Accession DisplayHelp Not logged in | LoginHelp
GEO help: Mouse over screen elements for information.
Series GSE205251 Query DataSets for GSE205251
Status Public on Jun 03, 2022
Title Melanoma GEMM Tumors, untreated or vemurafenib treated [bulk RNA-seq]
Organism Mus musculus
Experiment type Expression profiling by high throughput sequencing
Summary Emerging research suggests that multiple tumor compartments can influence treatment responsiveness and relapse, yet the search for therapeutic resistance mechanisms remains largely focused on acquired genomic alterations in cancer cells. Here, we show how treatment-induced changes occur in multiple tumor compartments during tumor relapse and can reduce benefit of follow-on therapies. By utilizing serial biopsies, next generation sequencing and single cell transcriptomics, we tracked the evolution of multiple cellular compartments within individual lesions during first-line treatment response, relapse and second-line therapeutic interventions in an autochthonous model of melanoma. We discovered that while treatment-relapsed tumors remained genetically stable, they converged on a shared resistance phenotype characterized by dramatic changes in tumor cell differentiation state, immune infiltration and extracellular matrix (ECM) composition. Similar alterations in tumor cell differentiation were also observed in more than half of our treatment-relapsed patient tumors. Tumor cell state changes were coincident with ECM remodeling and increased tumor stiffness, which alone was sufficient to alter tumor cell fate and reduce treatment responses in melanoma cell lines in vitro. Despite the absence of acquired mutations in the targeted pathway, resistant tumors showed significantly decreased responsiveness to second-line therapy intervention within the same pathway. The ability to preclinically model relapse and refractory settings - while capturing dynamics within and crosstalk between all relevant tumor compartments - provides a unique opportunity to better design and sequence appropriate clinical interventions.
Overall design bulk RNA-seq
This study is related to GSE126714.
Contributor(s) Juntilla MR, Nickles D
Citation(s) 30824837
Submission date Jun 01, 2022
Last update date Sep 05, 2022
Contact name Dorothee Nickles
Organization name Genentech
Street address 1 DNA Way
City South San Francisco
State/province CA
ZIP/Postal code 94080
Country USA
Platforms (1)
GPL17021 Illumina HiSeq 2500 (Mus musculus)
Samples (34)
GSM6209158 SAM17356779
GSM6209159 SAM17356778
GSM6209160 SAM17356777
This SubSeries is part of SuperSeries:
GSE205294 Melanoma GEMM Tumors, untreated or vemurafenib treated
BioProject PRJNA844272

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
GSE205251_NGS446_VemuResistMelanomaGEMM_counts_gene.tsv.gz 1.6 Mb (ftp)(http) TSV
SRA Run SelectorHelp
Raw data are available in SRA
Processed data are available on Series record

| NLM | NIH | GEO Help | Disclaimer | Accessibility |
NCBI Home NCBI Search NCBI SiteMap