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Somatically acquired hypomethylation of IGF2 in breast and colorectal cancer

Ito, Y and Koessler, T and Ibrahim, AEK and Rai, S and Vowler, SL and Abu-amero, S and Silva, AL and Maia, AT and Huddleston, JE and Uribe-lewis, S and Woodfine, K and Jagodic, M and Nativio, R and Dunning, A and Moore, G and Klenova, E and Bingham, S and Pharoah, PDP and Brenton, JD and Beck, S and Sandhu, MS and Murrell, A (2008) 'Somatically acquired hypomethylation of IGF2 in breast and colorectal cancer.' Human Molecular Genetics, 17 (17). 2633 - 2643. ISSN 0964-6906

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Abstract

The imprinted insulin-like growth factor 2 (IGF2) gene is expressed predominantly from the paternal allele. Loss of imprinting (LOI) associated with hypomethylation at the promoter proximal sequence (DMR0) of the IGF2 gene was proposed as a predisposing constitutive risk biomarker for colorectal cancer. We used pyrosequencing to assess whether IGF2 DMR0 methylation is either present constitutively prior to cancer or whether it is acquired tissue-specifically after the onset of cancer. DNA samples from tumour tissues and matched non-tumour tissues from 22 breast and 42 colorectal cancer patients as well as peripheral blood samples obtained from colorectal cancer patients [SEARCH (n = case 192, controls 96)], breast cancer patients [ABC (n = case 364, controls 96)] and the European Prospective Investigation of Cancer [EPIC-Norfolk (n = breast 228, colorectal 225, controls 895)] were analysed. The EPIC samples were collected 2-5 years prior to diagnosis of breast or colorectal cancer. IGF2 DMR0 methylation levels in tumours were lower than matched non-tumour tissue. Hypomethylation of DMR0 was detected in breast (33A%) and colorectal (80%) tumour tissues with a higher frequency than LOI indicating that methylation levels are a better indicator of cancer than LOI. In the EPIC population, the prevalence of IGF2 DMR0 hypomethylation was 9.5% and this correlated with increased age not cancer risk. Thus, IGF2 DMR0 hypomethylation occurs as an acquired tissue-specific somatic event rather than a constitutive innate epimutation. These results indicate that IGF2 DMR0 hypomethylation has diagnostic potential for colon cancer rather than value as a surrogate biomarker for constitutive LOI. © The Author 2008. Published by Oxford University Press. All rights reserved.

Item Type: Article
Subjects: R Medicine > RC Internal medicine > RC0254 Neoplasms. Tumors. Oncology (including Cancer)
Divisions: Faculty of Science and Health > Biological Sciences, School of
Depositing User: Jim Jamieson
Date Deposited: 06 Oct 2011 09:45
Last Modified: 23 Jan 2019 01:15
URI: http://repository.essex.ac.uk/id/eprint/843

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