Intra-gene DNA methylation variability is a clinically independent prognostic marker in women's cancers

Thomas E. Bartlett, Allison Jones, Ellen L. Goode, Brooke L. Fridley, Julie M. Cunningham, Els M.J.J. Berns, Elisabeth Wik, Helga B. Salvesen, Ben Davidson, Claes G. Trope, Sandrina Lambrechts, Ignace Vergote, Martin Widschwendter

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6 Scopus citations

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 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.

Original languageEnglish (US)
Article numbere0143178
JournalPloS one
Volume10
Issue number12
DOIs
StatePublished - Dec 1 2015

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • General

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    Bartlett, T. E., Jones, A., Goode, E. L., Fridley, B. L., Cunningham, J. M., Berns, E. M. J. J., Wik, E., Salvesen, H. B., Davidson, B., Trope, C. G., Lambrechts, S., Vergote, I., & Widschwendter, M. (2015). Intra-gene DNA methylation variability is a clinically independent prognostic marker in women's cancers. PloS one, 10(12), [e0143178]. https://doi.org/10.1371/journal.pone.0143178