| Title: |
MEDB-43. Development of a bioinformatics pipeline for identification of differential DNA methylation events associated with medulloblastoma relapse |
| Authors: |
Kui, Christopher; Richardson, Stacey; Schwalbe, Ed; Thompson, Dean; Keeling, Claire; Strathdee, Gordon; Dufour, Christelle; Bailey, Simon; Ramaswamy, Vijay; Clifford, Steven C; Hill, Rebecca M |
| Publisher Information: |
Oxford University Press |
| Publication Year: |
2022 |
| Collection: |
Northumbria University, Newcastle: Northumbria Research Link (NRL) |
| Subject Terms: |
C700 Molecular Biology; Biophysics and Biochemistry |
| Description: |
Relapsed medulloblastoma (rMB) is treatment-resistant and fatal in ~95% of cases. The epigenetic features of rMB, and any role as drivers of disease relapse/treatment-resistance have yet to be investigated. We therefore developed a pipeline to identify differentially methylated CpGs (DM-CpGs) and regions (DMRs) in a paired-rMB cohort. Our paired-rMB cohort (n=61, relapsed tumours matched with diagnosis counterparts) with available Illumina Methylation 450K/850K microarray data was processed in R-Studio. The packages Limma and DMRcate were used to perform a paired differential methylation analysis on a filtered selection of array probes (n=335,767), identifying DM-CpGs and DMRs with a 5% FDR. DMRs were further retained if they had a maximum-Δβ of >0.2 and correlated with locus-specific gene expression in a separate paired DNA-methylation array/RNA-seq cohort from medulloblastoma diagnosis samples (n=202). Finally, we created univariable Cox models to assess the prognostic potential of DM-CpGs/DMRs in an independent survival cohort of medulloblastoma diagnosis samples (n=498). Across the paired-rMB cohort, there were few significant differential methylation events initially identified at relapse (n=258 DM-CpGs, n=32 DMRs). Upon sub-analysis by molecular group, MBGroup4 (n=18 pairs) alone yielded significant findings (n=189 DM-CpGs, n=26 DMRs). Most changes involved hypermethylation events detected at relapse. Multiple DM-CpGs identified at relapse were prognostic for both overall and event-free survival when assessed in our independent cohort (n=22 whole cohort, n=13 Group 4, BH-adjusted p |
| Document Type: |
article in journal/newspaper |
| File Description: |
text |
| Language: |
English |
| ISSN: |
1522-8517 |
| Relation: |
https://nrl.northumbria.ac.uk/id/eprint/49505/1/noac079.417.pdf; Kui, Christopher, Richardson, Stacey, Schwalbe, Ed, Thompson, Dean, Keeling, Claire, Strathdee, Gordon, Dufour, Christelle, Bailey, Simon, Ramaswamy, Vijay, Clifford, Steven C and Hill, Rebecca M (2022) MEDB-43. Development of a bioinformatics pipeline for identification of differential DNA methylation events associated with medulloblastoma relapse. Neuro-Oncology, 24 (Supp_1). i115-i115. ISSN 1522-8517 |
| DOI: |
10.1093/neuonc/noac079.417 |
| Availability: |
https://nrl.northumbria.ac.uk/id/eprint/49505/; https://doi.org/10.1093/neuonc/noac079.417; https://nrl.northumbria.ac.uk/id/eprint/49505/1/noac079.417.pdf |
| Rights: |
cc_by_nc_4_0 |
| Accession Number: |
edsbas.CDDFDD24 |
| Database: |
BASE |