# Epigenomic alterations define lethal CIMP-positive ependymomas of infancy

Source: https://onco.cc/key-papers/paper-mack-nature/  
OnCo record `paper-mack-nature` (Key paper). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

Paper cited by one term page, indexed on Europe PMC as PubMed record 24553142 and published in Nature; the citing page links this DOI, which is how the record was matched.

## Summary

Ependymomas are common childhood brain tumours that occur throughout the nervous system, but are most common in the paediatric hindbrain. Current standard therapy comprises surgery and radiation, but not cytotoxic chemotherapy as it does not further increase survival. Whole-genome and whole-exome sequencing of 47 hindbrain ependymomas reveals an extremely low mutation rate, and zero significant recurrent somatic single nucleotide variants. Although devoid of recurrent single nucleotide variants and focal copy number aberrations, poor-prognosis hindbrain ependymomas exhibit a CpG island methylator phenotype. Transcriptional silencing driven by CpG methylation converges exclusively on targets of the Polycomb repressive complex 2 which represses expression of differentiation genes through trimethylation of H3K27. CpG island methylator phenotype-positive hindbrain ependymomas are responsive to clinical drugs that target either DNA or H3K27 methylation both in vitro and in vivo. We conclude that epigenetic modifiers are the first rational therapeutic candidates for this deadly malignancy, which is epigenetically deregulated but genetically bland.

Indexed on Europe PMC as PubMed record 24553142 (DOI 10.1038/nature13108). Matched by DOI alone: one term page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.

## Fields

- Kind: Key paper
- Last checked: 2026-09-22
- Tags: europepmc-ingest
- Journal: Nature
- Year: 2014
- DOI: 10.1038/nature13108
- Authors: Mack SC, Witt H, Piro RM, et al.
- What it means: One term page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.
- Caveats: Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper.

## Sources

- Nature 2014: https://doi.org/10.1038/nature13108
- PubMed: https://pubmed.ncbi.nlm.nih.gov/24553142/
- Europe PMC: https://europepmc.org/article/MED/24553142

## Connected records

- terms: [Epigenetic progenitor theory: cancer without a first mutation](https://onco.cc/terms/epigenetic-progenitor-theory/)
- journals: [Nature](https://onco.cc/journals/nature/)

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