GEO DataSets

(Submitter supplied) In this report, we generated eight matched pairs of vemurafenib sensitive/resistant melanoma lines and subjected these to concurrent RNA-seq and H3K27Ac ChIP-seq analysis. Globally, we identified two classes of epigenetic profiles that correlate with resistance. Class 1 resistance involves fewer RNA expression alterations accompanied by fewer enhancer mark changes with H3K27Ac. Class 2 resistance shows widespread alterations in transcription and enhancer profiles, which converge on EMT and hypoxia-related pathways. more...

Organism:

Homo sapiens

Type:

Expression profiling by high throughput sequencing

Platform:

GPL16791

16 Samples

Download data: CSV

(Submitter supplied) This SuperSeries is composed of the SubSeries listed below.

Organism:

Homo sapiens

Type:

Genome binding/occupancy profiling by high throughput sequencing; Expression profiling by high throughput sequencing

Platform:

GPL16791

48 Samples

Download data: BW, CSV

(Submitter supplied) In this report, we generated eight matched pairs of vemurafenib sensitive/resistant melanoma lines and subjected these to concurrent RNA-seq and H3K27Ac ChIP-seq analysis. Globally, we identified two classes of epigenetic profiles that correlate with resistance. Class 1 resistance involves fewer RNA expression alterations accompanied by fewer enhancer mark changes with H3K27Ac. Class 2 resistance shows widespread alterations in transcription and enhancer profiles, which converge on EMT and hypoxia-related pathways. more...

Organism:

Homo sapiens

Type:

Genome binding/occupancy profiling by high throughput sequencing

Platform:

GPL16791

32 Samples

Download data: BW

(Submitter supplied) Illumina HumanExon510S-DUO bead arrays (Illumina Inc) were performed according to the manufacturer's protocol.

Organism:

Homo sapiens

Type:

Genome variation profiling by SNP array; SNP genotyping by SNP array

Platform:

GPL6988

4 Samples

Download data: TXT

(Submitter supplied) Differential gene expression analysis of parental and resistant sub-lines of melanoma cell lines treated or untreated with PLX4032 Using microarray we sought to obtain a genome-wide profile of differentially expressed genes in parental melanoma cell lines and resistant sub-lines in response to PLX4032 vs DMSO control treatment.

Organism:

Homo sapiens

Type:

Expression profiling by array

Platform:

GPL6244

24 Samples

Download data: CEL, TXT

(Submitter supplied) Genome variation profiling of BRAFi resistant melanoma cell lines comapered to the original ones by Affymetrix CytoScan 750K microarray

Organism:

Homo sapiens

Type:

Genome variation profiling by SNP array; SNP genotyping by SNP array

Platform:

GPL18637

8 Samples

Download data: CEL, CYCHP

(Submitter supplied) We generated four drug-resistant melanoma cell lines from paired primary/metastatic cell lines using PLX4720 and used for Affymetrix Human Gene 1.0 ST array

Organism:

Homo sapiens

Type:

Expression profiling by array

Platform:

GPL6244

8 Samples

Download data: CEL

(Submitter supplied) The combination of JQ1 and Vemurafenib acted synergistically in BRAF-mutant cell lines, resulting in marked apoptosis in vitro, with up-regulation of pro-apoptotic proteins. In vivo, combination treatment suppressed tumor growth and significantly improved survival compared to either drug alone. RNA sequencing of tumor tissues revealed almost four thousand genes that were uniquely modulated by the combination, with several anti-apoptotic genes significantly down-regulated.

Organism:

Homo sapiens

Type:

Expression profiling by high throughput sequencing

Platform:

GPL11154

16 Samples

Download data: TXT

(Submitter supplied) We performed RNA-seq in parental MEL-XY3 melanoma cells (JM9) and in MEL-XY3 SUR cells obtained in vitro after 5 week treatment with PLX4032 (JM7)

Organism:

Homo sapiens

Type:

Expression profiling by high throughput sequencing

Platform:

GPL20301

2 Samples

Download data: XLSX

(Submitter supplied) A panel of 29 melanoma cell lines were gene expression profiled by RNA-Seq.

Organism:

Homo sapiens

Type:

Expression profiling by high throughput sequencing

Platform:

GPL11154

29 Samples

Download data: TXT

(Submitter supplied) Increased MITF expression contributes to melanoma progression and resistance to BRAF pathway inhibition. We show that, unexpectedly, lack of MITF is associated with more severe resistance to a range of inhibitors. Indeed, the presence of endogenous MITF was essential for robust drug responses. Both in primary and acquired resistance, MITF levels inversely correlated with expression of several activated receptor tyrosine kinases, most commonly AXL. more...

Organism:

Homo sapiens

Type:

Expression profiling by high throughput sequencing

Platform:

GPL11154

14 Samples

Download data: TXT

(Submitter supplied) Using a chromatin regulator-focused shRNA library, we found that suppression of sex determining region Y-box 10 (SOX10) in melanoma causes resistance to BRAF and MEK inhibitors. To investigate how SOX10 loss leads to drug resistance, we performed transcriptome sequencing (RNAseq) of both parental A375 (Ctrl. PLKO) and A375-SOX10KD (shSOX10-1, shSOX10-2) cells. To ask directly whether SOX10 is involved indrug resistance in BRAF(V600E) melanoma patients, we isolated RNA from paired biopsies from melanoma patients (pre- and post- treatment) , that had gained BRAF or MEK inhibitor resistance . more...

Organism:

Homo sapiens

Type:

Expression profiling by high throughput sequencing

Platform:

GPL11154

9 Samples

Download data: TXT

(Submitter supplied) About half of all melanomas harbor a constitutively active mutant BRAFV600E/K kinase that can be selectively inhibited by targeted BRAF inhibitors (BRAFi). While patients treated with BRAFi initially exhibit measurable clinical improvement, the majority of patients eventually develop drug resistance and relapse. We observe significant elevation of WNT5A in a subset of tumors from patients exhibiting disease progression on BRAFi therapy. more...

Organism:

Homo sapiens

Type:

Expression profiling by array

Platform:

GPL6480

10 Samples

Download data: TXT

(Submitter supplied) Colon cancer cell lines with partial sensitivity to the BRAF inhibitor PLX4720 were grown in increasing concentration of the drug to develop acquired resistance. Gene expression was performed for comparison of the resistant clones to the parental lines.

Organism:

Homo sapiens

Type:

Expression profiling by array

Dataset:

GDS4700

Platform:

GPL570

4 Samples

Download data: CEL

Analysis of HT29 and Colo205 parental colorectal cancer (CRC) cell lines and HT29 and Colo205 clones with acquired resistance to BRAF inhibitor PLX4720. BRAF is a protein kinase in the RAS/RAF/MEK/ERK pathway. Results provide insight into mechanisms of acquired resistance to BRAF inhibitors in CRC.

Organism:

Homo sapiens

Type:

Expression profiling by array, transformed count, 4 cell line sets

Platform:

GPL570

Series:

GSE34299

4 Samples

Download data: CEL

(Submitter supplied) The activation of transcriptional coactivators YAP and its paralog TAZ has been shown to promote resistance to anti-cancer therapies. YAP/TAZ activity is tightly coupled to actin cytoskeleton architecture. However, the influence of actin remodeling on cancer drug resistance remains largely unexplored. Here, we report a pivotal role of actin remodeling in YAP/TAZ-dependent BRAF inhibitor resistance in BRAF V600E mutant melanoma cells. more...

Organism:

Homo sapiens

Type:

Expression profiling by array

Platform:

GPL10558

16 Samples

Download data: IDAT, TXT

(Submitter supplied) Fifty percent of cutaneous melanomas are driven by activated BRAFV600E, but tumors treated with RAF inhibitors, even when they respond dramatically, rapidly adapt and develop resistance. Thus, there is a pressing need to identify the major mechanisms of intrinsic and adaptive resistance and develop drug combinations that target these resistance mechanisms. In a combinatorial drug screen on a panel of 12 treatment-naïve BRAFV600E mutant melanoma cell lines of varying levels of resistance to MAPK pathway inhibition we identified the combination PLX4720, a targeted inhibitor of mutated BRaf, and lapatinib, an inhibitor of the ERBB family of receptor tyrosine kinases, as synergistically cytotoxic in the subset of cell lines that displayed the most resistance to PLX4720. more...

Organism:

Homo sapiens

Type:

Expression profiling by array

Platform:

GPL10558

180 Samples

Download data

(Submitter supplied) Melanoma cell lines were assessed for differences in gene expression patterns between the lines sensitive and resistant to BRAF and MEK inhibitor drugs.

Organism:

Homo sapiens

Type:

Expression profiling by array

Platform:

GPL6244

46 Samples

Download data: CEL

(Submitter supplied) CGH profiling of M249 melanoma cell line treated with step-wise increasing Vemurafenib and Selumetinib to develop resistance (VSR). The resistance mechanims was through BRAF amplification in double minute (DM) format. The control cell line is untreated M249.

Organism:

Homo sapiens

Type:

Genome variation profiling by array

Platform:

GPL10152

2 Samples

Download data: TXT