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

Research output: Contribution to journalArticle

6 Citations (Scopus)

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

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DNA methylation
DNA Methylation
Genes
neoplasms
Neoplasms
genes
Biological Phenomena
Process Assessment (Health Care)
ovarian neoplasms
Ovarian Neoplasms
Tumors
Transcription Factors
transcription factors

ASJC Scopus subject areas

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

Cite this

Intra-gene DNA methylation variability is a clinically independent prognostic marker in women's cancers. / Bartlett, Thomas E.; Jones, Allison; Goode, Ellen L; Fridley, Brooke L.; Cunningham, Julie M; Berns, Els M J J; Wik, Elisabeth; Salvesen, Helga B.; Davidson, Ben; Trope, Claes G.; Lambrechts, Sandrina; Vergote, Ignace; Widschwendter, Martin.

In: PLoS One, Vol. 10, No. 12, e0143178, 01.12.2015.

Research output: Contribution to journalArticle

Bartlett, TE, Jones, A, Goode, EL, Fridley, BL, Cunningham, JM, Berns, EMJJ, Wik, E, Salvesen, HB, Davidson, B, Trope, CG, Lambrechts, S, Vergote, I & Widschwendter, M 2015, 'Intra-gene DNA methylation variability is a clinically independent prognostic marker in women's cancers', PLoS One, vol. 10, no. 12, e0143178. https://doi.org/10.1371/journal.pone.0143178
Bartlett, Thomas E. ; Jones, Allison ; Goode, Ellen L ; Fridley, Brooke L. ; Cunningham, Julie M ; Berns, Els M J J ; Wik, Elisabeth ; Salvesen, Helga B. ; Davidson, Ben ; Trope, Claes G. ; Lambrechts, Sandrina ; Vergote, Ignace ; Widschwendter, Martin. / Intra-gene DNA methylation variability is a clinically independent prognostic marker in women's cancers. In: PLoS One. 2015 ; Vol. 10, No. 12.
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