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Series GSE66295 Query DataSets for GSE66295
Status Public on Jul 14, 2015
Title A DNA Hypomethylation Signature Predicts Novel Anti-Tumor Activity of LSD1 Inhibitors in SCLC (BeadChip)
Organism Homo sapiens
Experiment type Methylation profiling by array
Summary Epigenetic dysregulation has emerged as an important mechanism in cancer. Alterations in epigenetic machinery have become a major focus for new targeted therapies. The current report describes the discovery and biological activity of a cyclopropylamine containing inhibitor of Lysine Demethylase 1 (LSD1), GSK2879552. This small molecule is a potent, selective, orally bioavailable, mechanism-based irreversible inhibitor of LSD1. A proliferation screen of cell lines representing a number of tumor types indicated that small cell lung carcinoma (SCLC) is sensitive to LSD1 inhibition. The subset of SCLC lines and primary samples that undergo growth inhibition in response to GSK2879552 exhibit DNA hypomethylation of a signature set of probes suggesting this may be used as a predictive biomarker of activity. The targeted mechanism coupled with a novel predictive biomarker make LSD1 inhibition an exciting potential therapy for SCLC, a highly prevalent, rarely cured, tumor type representing approximately 15% of all lung cancers.
Overall design DNA methylation profiling was performed using Infinium 450K methylation arrays on SCLC cell lines, patient derived xenografts, and patient samples. Data was processed and normalized using GenomeStudio V2011.1
Contributor(s) Mohammad HP, Smitheman K, Kamat CD, Soong D, Federowicz K, Van Aller G, Schneck J, Carson J, Liu Y, Butticello M, Bonnette W, Gorman S, Degenhardt Y, Bai Y, McCabe M, Pappalardi M, Kasparec J, Tian X, McNulty K, Rouse M, McDevitt P, Ho T, Crouthamel M, Concha N, McHugh C, Miller W, Dhanak D, Tummino P, Carpenter C, Johnson N, Hann C, Kruger RG
Citation(s) 26175415
Submission date Feb 25, 2015
Last update date Mar 22, 2019
Contact name David Soong
Organization name GlaxoSmithKline
Street address 1250 S Collegeville Rd
City Collegeville
State/province PA
ZIP/Postal code 19426
Country USA
Platforms (1)
GPL13534 Illumina HumanMethylation450 BeadChip (HumanMethylation450_15017482)
Samples (42)
GSM1618997 COLO668
GSM1618998 DMS 153
GSM1618999 DMS114
This SubSeries is part of SuperSeries:
GSE66298 A DNA Hypomethylation Signature Predicts Novel Anti-Tumor Activity of LSD1 Inhibitors in SCLC
BioProject PRJNA276452

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
GSE66295_GSM1618997-GSM1619027_signal_intensities.csv.gz 69.8 Mb (ftp)(http) CSV
GSE66295_RAW.tar 272.4 Mb (http)(custom) TAR (of IDAT)
Processed data included within Sample table

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