Bartlett, TE;
Jones, A;
Goode, EL;
Fridley, BL;
Cunningham, JM;
Berns, EM;
Wik, E;
... Widschwendter, M; + view all
(2015)
Intra-gene DNA methylation variability is a clinically independent prognostic marker in women's cancers.
PLoS One
, 10
(12)
, Article e0143178. 10.1371/journal.pone.0143178.
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Intra-gene DNA Methylation Variability is a Clinically Independent Prognostic Marker in Women's Cancers.pdf Download (3MB) | Preview |
Abstract
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 gene-panel 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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