Open Access Research article

DNA methylation alterations in grade II- and anaplastic pleomorphic xanthoastrocytoma

Ramón Martínez1*, F Javier Carmona6, Miguel Vizoso6, Veit Rohde1, Matthias Kirsch2, Gabriele Schackert2, Santiago Ropero3, Werner Paulus4, Alonso Barrantes5, Antonio Gomez6 and Manel Esteller678*

Author Affiliations

1 Department of Neurosurgery, University of Goettingen, Robert Koch. Str. 40, 37075 Goettingen, Germany

2 Department of Neurosurgery, University of Dresden, Fetscherstr. 74, 01307 Dresden, Germany

3 Department of Biochemistry and Molecular Biology, School of Medicine, University of Alcalá, Carretera Madrid-Barcelona Km. 33.6, 28871 Madrid, Spain

4 Institute of Neuropathology, University Hospital Muenster, Domagkstr. 17, 48149 Muenster, Germany

5 Institute of Neuropathology, University of Goettingen, Robert Koch. Str. 40, 37075 Goettingen, Germany

6 Cancer Epigenetics and Biology Program (PEBC), Bellvitge Biomedical Research Institute (IDIBELL), Hospital Duran i Reynals, Av. Gran Via de L’Hospitalet 199-203, 08907 Barcelona, Catalonia, Spain

7 Department of Physiological Sciences II, School of Medicine, University of Barcelona, 08907 Barcelona, Catalonia, Spain

8 Institució Catalana de Recerca i Estudis Avançats (ICREA), Barcelona, Catalonia, Spain

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BMC Cancer 2014, 14:213  doi:10.1186/1471-2407-14-213

Published: 20 March 2014

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.

Keywords:
Epigenetics; DNA methylation; Glioblastoma; Pleomorphic xanthoastrocyma