TY - JOUR
T1 - Intra-gene DNA methylation variability is a clinically independent prognostic marker in women's cancers
AU - Bartlett, Thomas E.
AU - Jones, Allison
AU - Goode, Ellen L.
AU - Fridley, Brooke L.
AU - Cunningham, Julie M.
AU - Berns, Els M.J.J.
AU - Wik, Elisabeth
AU - Salvesen, Helga B.
AU - Davidson, Ben
AU - Trope, Claes G.
AU - Lambrechts, Sandrina
AU - Vergote, Ignace
AU - Widschwendter, Martin
N1 - Funding Information:
This work was funded (MW, AJ) by the European Union''s Seventh Framework Programme (FP7/2007-2013) under grant agreement number 305428 (Project EpiFemCare), by the National Institute for Health Research University College London Hospitals Biomedical Research Centre, and by the Eve Appeal and the European Network Translational Research in Gynaecological Oncology (ENTRIGO) of the European Society of Gynaecological Oncology (ESGO). TEB received funding from the UK Engineering and Physical Sciences Research Council (ESPRC) and the UK Medical Research Council (MRC) via UCL CoMPLEX. ELG received funding from the Fred C. and Katherine B. Andersen Foundation, NIH grants R01-CA122443, P50-CA136393 (the Mayo Clinic Ovarian Cancer SPORE) and P30-CA15083. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Publisher Copyright:
© 2015 Bartlett et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
PY - 2015/12/1
Y1 - 2015/12/1
N2 - We introduce a novel per-gene measure of intra-gene DNA methylation variability (IGV) based on the Illumina Infinium HumanMethylation450 platform, which is prognostic independently of well-known predictors of clinical outcome. Using IGV, we derive a robust genepanel prognostic signature for ovarian cancer (OC, n = 221), which validates in two independent data sets from Mayo Clinic (n = 198) and TCGA (n = 358), with significance of p = 0.004 in both sets. The OC prognostic signature gene-panel is comprised of four gene groups, which represent distinct biological processes. We show the IGV measurements of these gene groups are most likely a reflection of a mixture of intra-tumour heterogeneity and transcription factor (TF) binding/activity. IGV can be used to predict clinical outcome in patients individually, providing a surrogate read-out of hard-to-measure disease processes.
AB - We introduce a novel per-gene measure of intra-gene DNA methylation variability (IGV) based on the Illumina Infinium HumanMethylation450 platform, which is prognostic independently of well-known predictors of clinical outcome. Using IGV, we derive a robust genepanel prognostic signature for ovarian cancer (OC, n = 221), which validates in two independent data sets from Mayo Clinic (n = 198) and TCGA (n = 358), with significance of p = 0.004 in both sets. The OC prognostic signature gene-panel is comprised of four gene groups, which represent distinct biological processes. We show the IGV measurements of these gene groups are most likely a reflection of a mixture of intra-tumour heterogeneity and transcription factor (TF) binding/activity. IGV can be used to predict clinical outcome in patients individually, providing a surrogate read-out of hard-to-measure disease processes.
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U2 - 10.1371/journal.pone.0143178
DO - 10.1371/journal.pone.0143178
M3 - Article
C2 - 26629914
AN - SCOPUS:84955485152
SN - 1932-6203
VL - 10
JO - PLoS One
JF - PLoS One
IS - 12
M1 - e0143178
ER -