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Series GSE79989 Query DataSets for GSE79989
Status Public on Dec 01, 2017
Title Massively-parallel functional characterization of MAPK1 missense mutants
Organism Homo sapiens
Experiment type Expression profiling by high throughput sequencing
Summary Genome-directed oncology has the potential to revolutionize patient treatment, but is limited by an abundance of rare, uncharacterized and therapeutically uninformative somatic variants. To accelerate characterization of the “long tail” of rare somatic variants, we quantified the activity and drug responsiveness of virtually all possible (99.84%) missense variants in the Ser/Thr kinase MAPK1/ERK2. We identified recurrent and rare hypermorphic and loss-of-function alleles, revealing that variant activity is uncorrelated with mutational frequency. Somatic ERK2 variants displayed variable responses to RAF-, MEK- and ERK-directed therapies, potentially informing clinical treatment strategies for patients whose tumors harbor these alterations. A subset of recurrent and rare somatic variants co-localized on ERK2 protein-protein interfaces, yet engendered contrasting phenotypes based on their specific sub-domain localization. The approach presented here represents an allele-characterization framework that compliments existing computational efforts and supports current and future somatic variant discovery efforts, advancing the promise of genome-guided treatment strategies.
Overall design Examination of the transcriptional output (mRNA) for a set of ERK2 Alleles under both trametinib drug treatment and DMSO controls. All experimental conditions were done in duplicates and sequenced in quadruplicates. Thus, each biological sample (48 total) was sequenced in 4 different lanes, resulting in total of 192 sequenced samples
Contributor(s) Brenan L, Cohen O, Cacchiarelli D, Johannessen CM
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Submission date Apr 06, 2016
Last update date May 15, 2019
Contact name Ofir Cohen
Phone 617-714-7301
Organization name Broad Institute
Department Cancer Program
Street address 415 Main St, Cambridge, MA 02142
City Cambridge
State/province Massachusetts
ZIP/Postal code 02142
Country USA
Platforms (1)
GPL18573 Illumina NextSeq 500 (Homo sapiens)
Samples (192)
GSM2242768 A375.1.1.A
GSM2242769 WT.1.1.A
GSM2242770 K54R.1.1.A
BioProject PRJNA330634
SRA SRP078984

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
GSE79989_ERK2_Alleles.Expression.reads.csv.gz 32.7 Mb (ftp)(http) CSV
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Raw data are available in SRA
Processed data are available on Series record

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