|
Status |
Public on May 25, 2022 |
Title |
Divergent BRAF Inhibitor Resistance Mechanisms Revealed through Epigenetic Mapping [RNA-seq] |
Organism |
Homo sapiens |
Experiment type |
Expression profiling by high throughput sequencing
|
Summary |
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. We also observed significant and dynamic changes in super-enhancers that underpin these transcriptomic patterns. We subsequently verified the 2-class structure in pre-BRAFi and post-relapse human melanoma specimens. Our findings reveal a broad and underappreciated spectrum of epigenetic plasticity during acquired BRAFi resistance.
|
|
|
Overall design |
Eight pairs of melanoma cell lines were subjected to RNAseq and ChIPseq.
|
Web link |
https://doi.org/10.1016/j.jid.2022.03.039
|
|
|
Contributor(s) |
Kang Y, Ji Z, Li H, Tsao H |
Citation(s) |
36529262 |
|
Submission date |
May 22, 2022 |
Last update date |
Jan 20, 2023 |
Contact name |
Hensin Tsao |
E-mail(s) |
htsao@mgh.harvard.edu
|
Organization name |
Massachusetts General Hospital
|
Street address |
50 Blossom St
|
City |
Boston |
State/province |
MA |
ZIP/Postal code |
02114 |
Country |
USA |
|
|
Platforms (1) |
GPL16791 |
Illumina HiSeq 2500 (Homo sapiens) |
|
Samples (16)
|
GSM6176118 |
SK-MEL-28, S (RNA-seq) |
GSM6176119 |
K4, P (RNA-seq) |
GSM6176120 |
K4, S (RNA-seq) |
GSM6176121 |
SK-MEL-37, P (RNA-seq) |
GSM6176122 |
SK-MEL-37, S (RNA-seq) |
GSM6176123 |
UACC903, P (RNA-seq) |
GSM6176124 |
UACC903, S (RNA-seq) |
GSM6176125 |
WM1205, P (RNA-seq) |
GSM6176126 |
WM1205, S (RNA-seq) |
GSM6176127 |
WM164, P (RNA-seq) |
GSM6176128 |
WM164, S (RNA-seq) |
GSM6176129 |
MGH-CH-1, P (RNA-seq) |
GSM6176130 |
MGH-CH-1, S (RNA-seq) |
|
This SubSeries is part of SuperSeries: |
GSE203546 |
Divergent BRAF Inhibitor Resistance Mechanisms Revealed through Epigenetic Mapping |
|
Relations |
BioProject |
PRJNA841360 |
Supplementary file |
Size |
Download |
File type/resource |
GSE203545_A375_logFC_1.csv.gz |
26.2 Kb |
(ftp)(http) |
CSV |
GSE203545_K4_logFC_1.csv.gz |
103.7 Kb |
(ftp)(http) |
CSV |
GSE203545_MGH-CH-1_logFC_1.csv.gz |
43.6 Kb |
(ftp)(http) |
CSV |
GSE203545_RAW.tar |
5.1 Mb |
(http)(custom) |
TAR (of CSV) |
GSE203545_SKmel-28_logFC_1.csv.gz |
110.5 Kb |
(ftp)(http) |
CSV |
GSE203545_SKmel-37_logFC_1.csv.gz |
47.2 Kb |
(ftp)(http) |
CSV |
GSE203545_UACC903_logFC_1.csv.gz |
134.1 Kb |
(ftp)(http) |
CSV |
GSE203545_WM1205_logFC_1.csv.gz |
25.6 Kb |
(ftp)(http) |
CSV |
GSE203545_WM164_logFC_1.csv.gz |
67.0 Kb |
(ftp)(http) |
CSV |
SRA Run Selector |
Raw data are available in SRA |
Processed data provided as supplementary file |
Processed data are available on Series record |