An Integrative Genomic and Epigenomic Approach for the Study of Transcriptional Regulation

Overview

Journal PLoS One

Specialties General Medicine
Science

Date 2008 Mar 28

PMID 18365023

Citations 41

Authors

Maria E Figueroa

Mark Reimers

Reid F Thompson

Kenny Ye

Yushan Li

Rebecca R Selzer

Jakob Fridriksson

Elisabeth Paietta

Peter Wiernik

Roland D Green

John M Greally

Ari Melnick

Affiliations

Soon will be listed here.

Abstract

The molecular heterogeneity of acute leukemias and other tumors constitutes a major obstacle towards understanding disease pathogenesis and developing new targeted-therapies. Aberrant gene regulation is a hallmark of cancer and plays a central role in determining tumor phenotype. We predicted that integration of different genome-wide epigenetic regulatory marks along with gene expression levels would provide greater power in capturing biological differences between leukemia subtypes. Gene expression, cytosine methylation and histone H3 lysine 9 (H3K9) acetylation were measured using high-density oligonucleotide microarrays in primary human acute myeloid leukemia (AML) and acute lymphocytic leukemia (ALL) specimens. We found that DNA methylation and H3K9 acetylation distinguished these leukemias of distinct cell lineage, as expected, but that an integrative analysis combining the information from each platform revealed hundreds of additional differentially expressed genes that were missed by gene expression arrays alone. This integrated analysis also enhanced the detection and statistical significance of biological pathways dysregulated in AML and ALL. Integrative epigenomic studies are thus feasible using clinical samples and provide superior detection of aberrant transcriptional programming than single-platform microarray studies.

Citing Articles

Promoter Methylation Status and Expression Levels of RASSF1A Gene in Different Phases of Acute Lymphoblastic Leukemia (ALL).

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Lactate-mediated epigenetic reprogramming regulates formation of human pancreatic cancer-associated fibroblasts.

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Genetics and epigenetics of pediatric leukemia in the era of precision medicine.

Ramos K, Ramos I, Zeng Y, Ramos K F1000Res. 2018; 7.

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Nonlinear Joint Latent Variable Models and Integrative Tumor Subtype Discovery.

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