Sequential DNA methylation changes are associated with DNMT3B overexpression in colorectal neoplastic progression

Ashraf E K Ibrahim; Mark J Arends; Ana-Luisa Silva; Andrew H Wyllie; Liliana Greger; Yoko Ito; Sarah L Vowler; Tim H-M Huang; Simon Tavaré; Adele Murrell; James D Brenton

doi:10.1136/gut.2010.223602

Sequential DNA methylation changes are associated with DNMT3B overexpression in colorectal neoplastic progression

Ashraf E K Ibrahim
, Mark J Arends
, Ana-Luisa Silva
, Andrew H Wyllie
, Liliana Greger
, Yoko Ito
, Sarah L Vowler
, Tim H-M Huang
, Simon Tavaré
, Adele Murrell
, James D Brenton

Department of Life Sciences

University of Cambridge

Research output: Contribution to journal › Article › peer-review

131 Citations (SciVal)

Abstract

Although aberrant methylation of key genes in the progression of colorectal neoplasia has been reported, no model-based analysis of the incremental changes through the intermediate adenoma stage has been described. In addition, the biological drivers for these methylation changes have yet to be defined. Linear mixed-effects modelling was used in this study to understand the onset and patterns of the methylation changes of SFRP2, IGF2 DMR0, H19, LINE-1 and a CpG island methylator phenotype (CIMP) marker panel, and they were correlated with DNA methyltransferase 3B (DNMT3B) levels of expression in a sample set representative of colorectal neoplastic progression.

Original language	English
Pages (from-to)	499-508
Number of pages	10
Journal	Gut
Volume	60
Issue number	4
DOIs	https://doi.org/10.1136/gut.2010.223602
Publication status	Published - Apr 2011

Keywords

Adenocarcinoma
Adenoma
Aged
Aged, 80 and over
Colon
Colonic Polyps
Colorectal Neoplasms
CpG Islands
DNA (Cytosine-5-)-Methyltransferase
DNA Methylation
DNA, Neoplasm
Disease Progression
Female
Humans
Hyperplasia
Insulin-Like Growth Factor II
Liver Neoplasms
Male
Membrane Proteins
Microsatellite Repeats
Middle Aged
Precancerous Conditions
Tumor Markers, Biological

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10.1136/gut.2010.223602

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title = "Sequential DNA methylation changes are associated with DNMT3B overexpression in colorectal neoplastic progression",

abstract = "Although aberrant methylation of key genes in the progression of colorectal neoplasia has been reported, no model-based analysis of the incremental changes through the intermediate adenoma stage has been described. In addition, the biological drivers for these methylation changes have yet to be defined. Linear mixed-effects modelling was used in this study to understand the onset and patterns of the methylation changes of SFRP2, IGF2 DMR0, H19, LINE-1 and a CpG island methylator phenotype (CIMP) marker panel, and they were correlated with DNA methyltransferase 3B (DNMT3B) levels of expression in a sample set representative of colorectal neoplastic progression.",

keywords = "Adenocarcinoma, Adenoma, Aged, Aged, 80 and over, Colon, Colonic Polyps, Colorectal Neoplasms, CpG Islands, DNA (Cytosine-5-)-Methyltransferase, DNA Methylation, DNA, Neoplasm, Disease Progression, Female, Humans, Hyperplasia, Insulin-Like Growth Factor II, Liver Neoplasms, Male, Membrane Proteins, Microsatellite Repeats, Middle Aged, Precancerous Conditions, Tumor Markers, Biological",

author = "Ibrahim, \{Ashraf E K\} and Arends, \{Mark J\} and Ana-Luisa Silva and Wyllie, \{Andrew H\} and Liliana Greger and Yoko Ito and Vowler, \{Sarah L\} and Huang, \{Tim H-M\} and Simon Tavar{\'e} and Adele Murrell and Brenton, \{James D\}",

year = "2011",

month = apr,

doi = "10.1136/gut.2010.223602",

language = "English",

volume = "60",

pages = "499--508",

journal = "Gut",

issn = "0017-5749",

publisher = "BMJ Publishing Group",

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TY - JOUR

T1 - Sequential DNA methylation changes are associated with DNMT3B overexpression in colorectal neoplastic progression

AU - Ibrahim, Ashraf E K

AU - Arends, Mark J

AU - Silva, Ana-Luisa

AU - Wyllie, Andrew H

AU - Greger, Liliana

AU - Ito, Yoko

AU - Vowler, Sarah L

AU - Huang, Tim H-M

AU - Tavaré, Simon

AU - Murrell, Adele

AU - Brenton, James D

PY - 2011/4

Y1 - 2011/4

N2 - Although aberrant methylation of key genes in the progression of colorectal neoplasia has been reported, no model-based analysis of the incremental changes through the intermediate adenoma stage has been described. In addition, the biological drivers for these methylation changes have yet to be defined. Linear mixed-effects modelling was used in this study to understand the onset and patterns of the methylation changes of SFRP2, IGF2 DMR0, H19, LINE-1 and a CpG island methylator phenotype (CIMP) marker panel, and they were correlated with DNA methyltransferase 3B (DNMT3B) levels of expression in a sample set representative of colorectal neoplastic progression.

AB - Although aberrant methylation of key genes in the progression of colorectal neoplasia has been reported, no model-based analysis of the incremental changes through the intermediate adenoma stage has been described. In addition, the biological drivers for these methylation changes have yet to be defined. Linear mixed-effects modelling was used in this study to understand the onset and patterns of the methylation changes of SFRP2, IGF2 DMR0, H19, LINE-1 and a CpG island methylator phenotype (CIMP) marker panel, and they were correlated with DNA methyltransferase 3B (DNMT3B) levels of expression in a sample set representative of colorectal neoplastic progression.

KW - Adenocarcinoma

KW - Adenoma

KW - Aged

KW - Aged, 80 and over

KW - Colon

KW - Colonic Polyps

KW - Colorectal Neoplasms

KW - CpG Islands

KW - DNA (Cytosine-5-)-Methyltransferase

KW - DNA Methylation

KW - DNA, Neoplasm

KW - Disease Progression

KW - Female

KW - Humans

KW - Hyperplasia

KW - Insulin-Like Growth Factor II

KW - Liver Neoplasms

KW - Male

KW - Membrane Proteins

KW - Microsatellite Repeats

KW - Middle Aged

KW - Precancerous Conditions

KW - Tumor Markers, Biological

UR - http://dx.doi.org/10.1136/gut.2010.223602

U2 - 10.1136/gut.2010.223602

DO - 10.1136/gut.2010.223602

M3 - Article

C2 - 21068132

SN - 0017-5749

VL - 60

SP - 499

EP - 508

JO - Gut

JF - Gut

IS - 4

ER -

Sequential DNA methylation changes are associated with DNMT3B overexpression in colorectal neoplastic progression

Abstract

Keywords

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