An integrative genomic and epigenomic approach for the study of transcriptional regulation.
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 i...
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doaj-8032ec1e5345484fbe6f573841a99a3f2020-11-24T21:50:35ZengPublic Library of Science (PLoS)PLoS ONE1932-62032008-03-0133e188210.1371/journal.pone.0001882An integrative genomic and epigenomic approach for the study of transcriptional regulation.Maria E FigueroaMark ReimersReid F ThompsonKenny YeYushan LiRebecca R SelzerJakob FridrikssonElisabeth PaiettaPeter WiernikRoland D GreenJohn M GreallyAri MelnickThe 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.http://europepmc.org/articles/PMC2266992?pdf=render |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
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 |
spellingShingle |
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 An integrative genomic and epigenomic approach for the study of transcriptional regulation. PLoS ONE |
author_facet |
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 |
author_sort |
Maria E Figueroa |
title |
An integrative genomic and epigenomic approach for the study of transcriptional regulation. |
title_short |
An integrative genomic and epigenomic approach for the study of transcriptional regulation. |
title_full |
An integrative genomic and epigenomic approach for the study of transcriptional regulation. |
title_fullStr |
An integrative genomic and epigenomic approach for the study of transcriptional regulation. |
title_full_unstemmed |
An integrative genomic and epigenomic approach for the study of transcriptional regulation. |
title_sort |
integrative genomic and epigenomic approach for the study of transcriptional regulation. |
publisher |
Public Library of Science (PLoS) |
series |
PLoS ONE |
issn |
1932-6203 |
publishDate |
2008-03-01 |
description |
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. |
url |
http://europepmc.org/articles/PMC2266992?pdf=render |
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