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Published in: BMC Cancer 1/2014

Open Access 01-12-2014 | Research article

DNA methylation alterations in grade II- and anaplastic pleomorphic xanthoastrocytoma

Authors: Ramón Martínez, F Javier Carmona, Miguel Vizoso, Veit Rohde, Matthias Kirsch, Gabriele Schackert, Santiago Ropero, Werner Paulus, Alonso Barrantes, Antonio Gomez, Manel Esteller

Published in: BMC Cancer | Issue 1/2014

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Abstract

Background

Pleomorphic xanthoastrocytoma (PXA) is a rare WHO grade II tumor accounting for less than 1% of all astrocytomas. Malignant transformation into PXA with anaplastic features, is unusual and correlates with poorer outcome of the patients.

Methods

Using a DNA methylation custom array, we have quantified the DNA methylation level on the promoter sequence of 807 cancer-related genes of WHO grade II (n = 11) and III PXA (n = 2) and compared to normal brain tissue (n = 10) and glioblastoma (n = 87) samples. DNA methylation levels were further confirmed on independent samples by pyrosequencing of the promoter sequences.

Results

Increasing DNA promoter hypermethylation events were observed in anaplastic PXA as compared with grade II samples. We further validated differential hypermethylation of CD81, HCK, HOXA5, ASCL2 and TES on anaplastic PXA and grade II tumors. Moreover, these epigenetic alterations overlap those described in glioblastoma patients, suggesting common mechanisms of tumorigenesis.

Conclusions

Even taking into consideration the small size of our patient populations, our data strongly suggest that epigenome-wide profiling of PXA is a valuable tool to identify methylated genes, which may play a role in the malignant progression of PXA. These methylation alterations may provide useful biomarkers for decision-making in those patients with low-grade PXA displaying a high risk of malignant transformation.
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Metadata
Title
DNA methylation alterations in grade II- and anaplastic pleomorphic xanthoastrocytoma
Authors
Ramón Martínez
F Javier Carmona
Miguel Vizoso
Veit Rohde
Matthias Kirsch
Gabriele Schackert
Santiago Ropero
Werner Paulus
Alonso Barrantes
Antonio Gomez
Manel Esteller
Publication date
01-12-2014
Publisher
BioMed Central
Published in
BMC Cancer / Issue 1/2014
Electronic ISSN: 1471-2407
DOI
https://doi.org/10.1186/1471-2407-14-213

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