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 - 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 -