Cardiff University | Prifysgol Caerdydd ORCA
Online Research @ Cardiff 
WelshClear Cookie - decide language by browser settings

Methylome analysis identifies a Wilms tumor epigenetic biomarker detectable in blood

Charlton, Jocelyn, Williams, Richard D, Weeks, Mark, Sebire, Neil J, Popov, Sergey, Vujanic, Gordan, Mifsud, William, Alcaide-German, Marisa, Butcher, Lee M, Beck, Stephan and Pritchard-Jones, Kathy 2014. Methylome analysis identifies a Wilms tumor epigenetic biomarker detectable in blood. Genome Biology 15 (8) 10.1186/s13059-014-0434-y

Full text not available from this repository.

Abstract

Background Wilms tumor is the most common pediatric renal malignancy and there is a clinical need for a molecular biomarker to assess treatment response and predict relapse. The known mutated genes in this tumor type show low mutation frequencies, whereas aberrant methylation at 11p15 is by far the most common aberration. We therefore analyzed the epigenome, rather than the genome, to identify ubiquitous tumor-specific biomarkers. Results Methylome analysis of matched normal kidney and Wilms tumor identifies 309 preliminary methylation variable positions which we translate into three differentially methylated regions (DMRs) for use as tumor-specific biomarkers. Using two novel algorithms we show that these three DMRs are not confounded by cell type composition. We further show that these DMRs are not methylated in embryonic blastema but are intermediately methylated in Wilms tumor precursor lesions. We validate the biomarker DMRs using two independent sample sets of normal kidney and Wilms tumor and seven Wilms tumor histological subtypes, achieving 100% and 98% correct classification, respectively. As proof-of-principle for clinical utility, we successfully use biomarker DMR-2 in a pilot analysis of cell-free circulating DNA to monitor tumor response during treatment in ten patients. Conclusions These findings define the most common methylated regions in Wilms tumor known to date which are not associated with their embryonic origin or precursor stage. We show that this tumor-specific methylated DNA is released into the blood circulation where it can be detected non-invasively showing potential for clinical utility.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Medicine
Subjects: R Medicine > R Medicine (General)
R Medicine > RC Internal medicine > RC0254 Neoplasms. Tumors. Oncology (including Cancer)
Publisher: BioMed Central
ISSN: 1474-760X
Date of Acceptance: 8 August 2014
Last Modified: 31 May 2019 15:05
URI: http://orca.cf.ac.uk/id/eprint/88218

Citation Data

Cited 11 times in Google Scholar. View in Google Scholar

Cited 16 times in Scopus. View in Scopus. Powered By Scopus® Data

Actions (repository staff only)

Edit Item Edit Item