Intra-Gene DNA Methylation Variability Is a Clinically Independent Prognostic Marker in Women's Cancers.
oleh: 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
| Format: | Article |
|---|---|
| Diterbitkan: | Public Library of Science (PLoS) 2015-01-01 |
Deskripsi
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.