1. Correction to: DNA methylation signature is prognostic of choroid plexus tumor aggressiveness
- Author
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Cynthia Hawkins, Christian Thomas, Diana M. Merino, Michael Brudno, Eric Bouffet, Tanya Guha, David Malkin, Adam Shlien, Jonathan L. Finlay, Sanaa Choufani, Rosanna Weksberg, Martin Sill, Richard J. Gilbertson, Martin Hasselblatt, David Capper, Andrei L. Turinsky, Uri Tabori, Nada Jabado, Malgorzata Pienkowska, and Ana Novokmet
- Subjects
0301 basic medicine ,Epigenomics ,Choroid Plexus Neoplasms ,Biology ,Epigenesis, Genetic ,Diagnosis, Differential ,03 medical and health sciences ,0302 clinical medicine ,Genetics ,medicine ,Biomarkers, Tumor ,Humans ,Phospholipid Transfer Proteins ,Choroid plexus tumor ,Molecular Biology ,Genetics (clinical) ,Adenylate Kinase ,Carcinoma ,Correction ,Period Circadian Proteins ,DNA Methylation ,medicine.disease ,Prognosis ,Survival Analysis ,Human genetics ,030104 developmental biology ,030220 oncology & carcinogenesis ,DNA methylation ,Mutation ,Cancer research ,CpG Islands ,Papilloma, Choroid Plexus ,Tumor Suppressor Protein p53 ,Developmental Biology - Abstract
Histological grading of choroid plexus tumors (CPTs) remains the best prognostic tool to distinguish between aggressive choroid plexus carcinoma (CPC) and the more benign choroid plexus papilloma (CPP) or atypical choroid plexus papilloma (aCPP); however, these distinctions can be challenging. Standard treatment of CPC is very aggressive and often leads to severe damage to the young child's brain. Therefore, it is crucial to distinguish between CPC and less aggressive entities (CPP or aCPP) to avoid unnecessary exposure of the young patient to neurotoxic therapy. To better stratify CPTs, we utilized DNA methylation (DNAm) to identify prognostic epigenetic biomarkers for CPCs.We obtained DNA methylation profiles of 34 CPTs using the HumanMethylation450 BeadChip from Illumina, and the data was analyzed using the Illumina Genome Studio analysis software. Validation of differentially methylated CpG sites chosen as biomarkers was performed using pyrosequencing analysis on additional 22 CPTs. Sensitivity testing of the CPC DNAm signature was performed on a replication cohort of 61 CPT tumors obtained from Neuropathology, University Hospital Münster, Germany.Generated genome-wide DNAm profiles of CPTs showed significant differences in DNAm between CPCs and the CPPs or aCPPs. The prediction of clinical outcome could be improved by combining the DNAm profile with the mutational status of TP53. CPCs with homozygous TP53 mutations clustered as a group separate from those carrying a heterozygous TP53 mutation or CPCs with wild type TP53 (TP53-wt) and showed the worst survival outcome. Specific DNAm signatures for CPCs revealed AK1, PER2, and PLSCR4 as potential biomarkers for CPC that can be used to improve molecular stratification for diagnosis and treatment.We demonstrate that combining specific DNAm signature for CPCs with histological approaches better differentiate aggressive tumors from those that are not life threatening. These findings have important implications for future prognostic risk prediction in clinical disease management.
- Published
- 2019