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A DNA Hypomethylation Signature Predicts Novel Anti-Tumor Activity of LSD1 Inhibitors in SCLC

ABSTRACT: This SuperSeries is composed of the SubSeries listed below. Refer to individual Series

ORGANISM(S): Homo sapiens

SUBMITTER: David Soong

PROVIDER: E-GEOD-66298 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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A DNA Hypomethylation Signature Predicts Antitumor Activity of LSD1 Inhibitors in SCLC.

Mohammad Helai P HP Smitheman Kimberly N KN Kamat Chandrashekhar D CD Soong David D Federowicz Kelly E KE Van Aller Glenn S GS Schneck Jess L JL Carson Jeffrey D JD Liu Yan Y Butticello Michael M Bonnette William G WG Gorman Shelby A SA Degenhardt Yan Y Bai Yuchen Y McCabe Michael T MT Pappalardi Melissa B MB Kasparec Jiri J Tian Xinrong X McNulty Kenneth C KC Rouse Meagan M McDevitt Patrick P Ho Thau T Crouthamel Michelle M Hart Timothy K TK Concha Nestor O NO McHugh Charles F CF Miller William H WH Dhanak Dashyant D Tummino Peter J PJ Carpenter Christopher L CL Johnson Neil W NW Hann Christine L CL Kruger Ryan G RG

Cancer cell 20150701 1

Epigenetic dysregulation has emerged as an important mechanism in cancer. Alterations in epigenetic machinery have become a major focus for 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 inactivator of LSD1. A proliferation screen of cell lines representing a number of tumor typ ...[more]

PMID: 26175415

Similar Datasets

A DNA Hypomethylation Signature Predicts Novel Anti-Tumor Activity of LSD1 Inhibitors in SCLC (BeadChip)

Project description: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. 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

2015-07-14 | E-GEOD-66295 | biostudies-arrayexpress

Methylation Profiling of Human Kidney Tubules

Project description:We sought to decrease the cell type heterogeneity of kidney tissues to increase the resolution of methylation profiles. To that end, microdissected human kidney tissue from patients are used and hybridized on Illumina HumanMethylation450 BeadChip arrays. We extract genomic DNA from microdissected human kidney tubule samples. And used these genomic DNA for the Illumina 450K beads array.

2013-09-14 | E-GEOD-50874 | biostudies-arrayexpress

Genome-wide DNA methylation analysis of human brain tissue from schizophrenia patients

Project description:Recent studies suggest that genetic and environmental factors do not account for all the schizophrenia risk and epigenetics also plays a role in disease susceptibility. DNA methylation is a heritable epigenetic modification that can regulate gene expression. Genome-Wide DNA methylation analysis was performed on post-mortem human brain tissue from 24 patients with schizophrenia and 24 unaffected controls. DNA methylation was assessed at over 485 000 CpG sites using the Illumina Infinium Human Methylation450 Bead Chip. After adjusting for age and post-mortem interval (PMI), 4 641 probes corresponding to 2 929 unique genes were found to be differentially methylated. Of those genes, 1 291 were located in a CpG island and 817 were in a promoter region. These include NOS1, AKT1, DTNBP1, DNMT1, PPP3CC and SOX10 which have previously been associated with schizophrenia. More than 100 of these genes overlap with a previous DNA methylation study of peripheral blood from schizophrenia patients in which 27 000 CpG sites were analysed. Unsupervised clustering analysis of the top 3 000 most variable probes revealed two distinct groups with significantly more people with schizophrenia in cluster one compared to controls (p = 1.74x10-4). The first cluster was composed of 88% of patients with schizophrenia and only 12% controls while the second cluster was composed of 27% of patients with schizophrenia and 73% controls. These results strongly suggest that differential DNA methylation is important in schizophrenia etiology and add support for the use of DNA methylation profiles as a future prognostic indicator of schizophrenia Genome-Wide DNA methylation analysis was performed on post-mortem human brain tissue from 24 patients with schizophrenia and 24 unaffected controls. DNA methylation was assessed at over 485 000 CpG sites using the Illumina Infinium Human Methylation450 Bead Chip.

2014-09-05 | E-GEOD-61107 | biostudies-arrayexpress

Genome-wide Scan for Methylation Profiles in Breast Cancer

Project description:Genome wide DNA methylation profiling of normal and breast cancer samples. The Illumina Infinium 450k Human DNA methylation Beadchip v1.1 was used to obtain DNA methylation profiles across approximately 485577 CpGs in breast cancer and normal samples. Samples included 40 normal, 80 breast cancer samples. Bisulphite converted DNA from the 120 samples were hybridised to the Illumina Infinium 450k Human Methylation Beadchip v1.1

2015-03-11 | E-GEOD-66695 | biostudies-arrayexpress

Stress, heritability, tissue type and human methylome variation.

Project description:Genomewide methylation profiles from three tissues (cord blood, placenta, venous blood) derived from 24 mother-child dyads. Data was assayed with the Illumina HumanMethylation 450K Beacdchip and processed with Illumina's GenomeStudio V2011.1 Methylation Module v1.9.0 Bisulfite converted DNA from three tissues derived from 24 dyads, totalling 72 samples, were hybridized to the Illumina HumanMethylation450 BeadChips following the manufacturerÕs specifications.

2014-03-01 | E-GEOD-54399 | biostudies-arrayexpress

DNA methylation screening of small bowel adenocarcinoma

Project description:Illumina Infinium 450k screening of normal and tumour tissue in a retrospective 28 sample cohort of small bowel adenocarcinoma patients. Average signal and beta values normalised to internal Illumina controls. Comparing DNA methylation differences in a matched normal tumour cohort of 28 small bowel adenocarcinoma patients.

2015-09-03 | E-GEOD-61467 | biostudies-arrayexpress

COHCAP: City of Hope CpG Island Analysis Pipeline

Project description:COHCAP (City of Hope CpG Island Analysis Pipeline) is an algorithm to analyze single-nucleotide resolution DNA methylation data. It provides QC metrics, differential methylation for CpG Sites, differential methylation for CpG Islands, integration with gene expression data, and visualization of methylation values. COHCAP is currently the only DNA methylation package that can handle integration with gene expression data, and the results of this study show that COHCAP can identify regions of differential methylation with ~50% concordance with gene expression. COHCAP is scalable for analysis of both cell line data and heterogeneous patient data, and it can identify known cancer biomarkers as well as intriguing new roles of epigenetic regulation in cancer (such as methylation of estrogen receptor in breast cancer patients). This study also uses cell line data to show that COHCAP is capable of analyzing Illumina methylation array and targeted bisulfite sequencing data, with either 1-group or 2-group study designs. The accuracy of COHCAP is accessed using qPCR, EpiTect, and comparison of COHCAP regions of differential methylation with MIRA peaks. This software is freely available at https://sourceforge.net/projects/cohcap/. The following third-party datasets were utilized in the paper: BS-Seq data: GSE26826 Additional Microarray Data: GSE29290 This SuperSeries is composed of the SubSeries listed below. Refer to individual Series.

2013-06-08 | E-GEOD-42310 | biostudies-arrayexpress

A minimal DNA 5-methylcytosine signature of oral tongue squamous cell carcinoma

Project description:This SuperSeries is composed of the SubSeries listed below. Refer to individual Series

2016-06-01 | E-GEOD-75540 | biostudies-arrayexpress

Sex differences of leukocytes DNA methylation

Project description:Genome wide DNA methylation profiling of peripheral blood samples. The Illumina Infinium 450k Human DNA methylation Beadchip was used to obtain DNA methylation profiles across approximately 450,000 CpGs. Samples included 63 of male samples,and 54 of female samples from peripheral leukocytes. All samples were healthy controls. Bisulphite converted DNA from the 117 samples were hybridised to the Illumina Infinium 450k Human Methylation Beadchip. Samples 1-93 were used in a pilot experiment and Samples 101-124 were used in a replicated experiment.

2016-03-01 | E-GEOD-67393 | biostudies-arrayexpress

Genome-wide Scan for Methylation Profiles in Keloids

Project description:Genome wide DNA methylation profiling of normal skin and keloid samples. The Illumina Infinium 450k Human DNA methylation Beadchip v1.1 was used to obtain DNA methylation profiles across approximately 485577 CpGs in keloid and normal samples. Samples included 6 normal skin, 6 Keloid. Bisulphite converted DNA from the 12 samples were hybridised to the Illumina Infinium 450k Human Methylation Beadchip v1.1

2014-04-02 | E-GEOD-56420 | biostudies-arrayexpress

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