Cargando…

DNA methylation alterations in grade II- and anaplastic pleomorphic xanthoastrocytoma

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 h...

Descripción completa

Detalles Bibliográficos
Autores principales: Martínez, Ramón, Carmona, F Javier, Vizoso, Miguel, Rohde, Veit, Kirsch, Matthias, Schackert, Gabriele, Ropero, Santiago, Paulus, Werner, Barrantes, Alonso, Gomez, Antonio, Esteller, Manel
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4000050/
https://www.ncbi.nlm.nih.gov/pubmed/24650279
http://dx.doi.org/10.1186/1471-2407-14-213
_version_ 1782313571504357376
author Martínez, Ramón
Carmona, F Javier
Vizoso, Miguel
Rohde, Veit
Kirsch, Matthias
Schackert, Gabriele
Ropero, Santiago
Paulus, Werner
Barrantes, Alonso
Gomez, Antonio
Esteller, Manel
author_facet Martínez, Ramón
Carmona, F Javier
Vizoso, Miguel
Rohde, Veit
Kirsch, Matthias
Schackert, Gabriele
Ropero, Santiago
Paulus, Werner
Barrantes, Alonso
Gomez, Antonio
Esteller, Manel
author_sort Martínez, Ramón
collection PubMed
description 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.
format Online
Article
Text
id pubmed-4000050
institution National Center for Biotechnology Information
language English
publishDate 2014
publisher BioMed Central
record_format MEDLINE/PubMed
spelling pubmed-40000502014-04-26 DNA methylation alterations in grade II- and anaplastic pleomorphic xanthoastrocytoma Martínez, Ramón Carmona, F Javier Vizoso, Miguel Rohde, Veit Kirsch, Matthias Schackert, Gabriele Ropero, Santiago Paulus, Werner Barrantes, Alonso Gomez, Antonio Esteller, Manel BMC Cancer Research Article 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. BioMed Central 2014-03-20 /pmc/articles/PMC4000050/ /pubmed/24650279 http://dx.doi.org/10.1186/1471-2407-14-213 Text en Copyright © 2014 Martínez et al.; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research Article
Martínez, Ramón
Carmona, F Javier
Vizoso, Miguel
Rohde, Veit
Kirsch, Matthias
Schackert, Gabriele
Ropero, Santiago
Paulus, Werner
Barrantes, Alonso
Gomez, Antonio
Esteller, Manel
DNA methylation alterations in grade II- and anaplastic pleomorphic xanthoastrocytoma
title DNA methylation alterations in grade II- and anaplastic pleomorphic xanthoastrocytoma
title_full DNA methylation alterations in grade II- and anaplastic pleomorphic xanthoastrocytoma
title_fullStr DNA methylation alterations in grade II- and anaplastic pleomorphic xanthoastrocytoma
title_full_unstemmed DNA methylation alterations in grade II- and anaplastic pleomorphic xanthoastrocytoma
title_short DNA methylation alterations in grade II- and anaplastic pleomorphic xanthoastrocytoma
title_sort dna methylation alterations in grade ii- and anaplastic pleomorphic xanthoastrocytoma
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4000050/
https://www.ncbi.nlm.nih.gov/pubmed/24650279
http://dx.doi.org/10.1186/1471-2407-14-213
work_keys_str_mv AT martinezramon dnamethylationalterationsingradeiiandanaplasticpleomorphicxanthoastrocytoma
AT carmonafjavier dnamethylationalterationsingradeiiandanaplasticpleomorphicxanthoastrocytoma
AT vizosomiguel dnamethylationalterationsingradeiiandanaplasticpleomorphicxanthoastrocytoma
AT rohdeveit dnamethylationalterationsingradeiiandanaplasticpleomorphicxanthoastrocytoma
AT kirschmatthias dnamethylationalterationsingradeiiandanaplasticpleomorphicxanthoastrocytoma
AT schackertgabriele dnamethylationalterationsingradeiiandanaplasticpleomorphicxanthoastrocytoma
AT roperosantiago dnamethylationalterationsingradeiiandanaplasticpleomorphicxanthoastrocytoma
AT pauluswerner dnamethylationalterationsingradeiiandanaplasticpleomorphicxanthoastrocytoma
AT barrantesalonso dnamethylationalterationsingradeiiandanaplasticpleomorphicxanthoastrocytoma
AT gomezantonio dnamethylationalterationsingradeiiandanaplasticpleomorphicxanthoastrocytoma
AT estellermanel dnamethylationalterationsingradeiiandanaplasticpleomorphicxanthoastrocytoma