Dataset Information

Preneoplastic Alterations Define CLL DNA Methylome and Persist through Disease Progression and Therapy.

ABSTRACT: Most human cancers converge to a deregulated methylome with reduced global levels and elevated methylation at select CpG islands. To investigate the emergence and dynamics of the cancer methylome, we characterized genome-wide DNA methylation in pre-neoplastic monoclonal B cell lymphocytosis (MBL) and chronic lymphocytic leukemia (CLL), including serial samples collected across disease course. We detected the aberrant tumor-associated methylation landscape at CLL diagnosis and found no significantly differentially methylated regions in the high-count MBL-to-CLL transition. Patient methylomes showed remarkable stability with natural disease and post-therapy progression. Single CLL cells were consistently aberrantly methylated, indicating a homogeneous transition to the altered epigenetic state, and a distinct expression profile together with MBL cells compared to normal B cells. Our longitudinal analysis reveals the cancer methylome to emerge early, which may provide a platform for subsequent genetically-driven growth dynamics and together with its persistent presence suggests a central role in the normal-to-cancer transition.

SUBMITTER: Kretzmer H

PROVIDER: S-EPMC7888194 | biostudies-literature | 2021 Jan

REPOSITORIES: biostudies-literature

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Preneoplastic Alterations Define CLL DNA Methylome and Persist through Disease Progression and Therapy.

Kretzmer Helene H Biran Anat A Purroy Noelia N Lemvigh Camilla K CK Clement Kendell K Gruber Michaela M Gu Hongcang H Rassenti Laura L Mohammad Arman W AW Lesnick Connie C Slager Susan L SL Braggio Esteban E Shanafelt Tait D TD Kay Neil E NE Fernandes Stacey M SM Brown Jennifer R JR Wang Lili L Li Shuqiang S Livak Kenneth J KJ Neuberg Donna S DS Klages Sven S Timmermann Bernd B Kipps Thomas J TJ Campo Elias E Gnirke Andreas A Wu Catherine J CJ Meissner Alexander A

Blood cancer discovery 20201203 1

Most human cancers converge to a deregulated methylome with reduced global levels and elevated methylation at select CpG islands. To investigate the emergence and dynamics of the cancer methylome, we characterized genome-wide DNA methylation in pre-neoplastic monoclonal B cell lymphocytosis (MBL) and chronic lymphocytic leukemia (CLL), including serial samples collected across disease course. We detected the aberrant tumor-associated methylation landscape at CLL diagnosis and found no significan ...[more]

PMID: 33604581

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Project description:Acute coronary syndrome (ACS) is a common disease with high mortality and morbidity rates. The methylation status of blood DNA may serve as a potential early diagnosis and prevention biomarker for numerous diseases. The present study was designed to explore novel genome-wide aberrant DNA methylation patterns associated with ACS. The Infinium HumanMethylation450 assay was used to examine genome-wide DNA methylation profiles in 3 pairs of ACS and control group samples. Epigenome-wide DNA methylation, genomic distribution, Gene Ontology (GO) term and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed. The results were confirmed using methylation-specific polymerase chain reaction (MSP) and Sequenom MassARRAY analyses in ACS, stable coronary artery disease (SCAD) and control samples. A total of 11,342 differentially methylated (DM) 5'-C-phosphate-G-3' (CpG) sites were identified, including 8,865 hypomethylated and 2,477 hypermethylated CpG sites in the ACS group compared with the control samples. They varied in frequency across genomic compartments, but were particularly notable in gene bodies and shores. The results of GO term and KEGG pathway enrichment analyses revealed that the methylated genes were associated with certain biological processes and pathways. Despite the considerable variability in methylation data, the candidate selected possessed significant methylation alteration in mothers against decapentaplegic homolog 3 (SMAD3) transcription start site 155 (Chr1:67356838-Chr1:67356942). MSP analysis from 81 ACS samples, 74 SCAD samples and 53 healthy samples, and Sequenom MassARRAY analysis, confirmed that differential CpG methylation of SMAD3 was significantly corrected with the reference results of the HumanMethylation450 array. The data identified an ACS-specific DNA methylation profile with a large number of novel DM CpG sites, some of which may serve as candidate markers for the early diagnosis of ACS.

Dataset Information

Preneoplastic Alterations Define CLL DNA Methylome and Persist through Disease Progression and Therapy.

Publications

Preneoplastic Alterations Define CLL DNA Methylome and Persist through Disease Progression and Therapy.

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