Loss of pericentromeric DNA methylation pattern in human glioblastoma is associated with altered DNA methyltransferases expression and involves the stem cell compartment

Ruggero De Maria Marchiano, M. Fanelli, S. Caprodossi, L. Ricci-Vitiani, A. Porcellini, F. Tomassoni-Ardori, S. Amatori, F. Andreoni, M. Magnani, A. Santoni, S. Minucci, P. G. Pelicci

Risultato della ricerca: Contributo in rivistaArticolo in rivista

54 Citazioni (Scopus)

Abstract

Cancer is generally characterized by loss of CG dinucleotides methylation resulting in a global hypomethylation and the consequent genomic instability. The major contribution to the general decreased methylation levels seems to be due to demethylation of heterochromatin repetitive DNA sequences. In human immunodeficiency, centromeric instability and facial anomalies syndrome, demethylation of pericentromeric satellite 2 DNA sequences has been correlated to functional mutations of the de novo DNA methyltransferase 3b (DNMT3b), but the mechanism responsible for the hypomethylated status in tumors is poorly known. Here, we report that human glioblastoma is affected by strong hypomethylation of satellite 2 pericentromeric sequences that involves the stem cell compartment. Concomitantly with the integrity of the DNMTs coding sequences, we report aberrations in DNA methyltrasferases expression showing upregulation of the DNA methyltransferase 1 (DNMT1) and downregulation of the de novo DNA methyltransferase 3a (DNMT3a). Moreover, we show that DNMT3a is the major de novo methyltransferase expressed in normal neural progenitor cells (NPCs) and its forced re-expression is sufficient to partially recover the methylation levels of satellite 2 repeats in glioblastoma cell lines. Thus, we speculate that DNMT3a decreased expression may be involved in the early post-natal inheritance of an epigenetically altered NPC population that could be responsible for glioblastoma development later in adult life. © 2008 Nature Publishing Group All rights reserved.
Lingua originaleEnglish
pagine (da-a)358-365
Numero di pagine8
RivistaOncogene
Volume27
DOI
Stato di pubblicazionePubblicato - 2008

Keywords

  • Brain Neoplasms
  • Brain tumor
  • Cancer Research
  • Cell Line, Tumor
  • DNA (Cytosine-5-)-Methyltransferases
  • DNA Methylation
  • DNA methylation
  • DNA methyltransferases
  • DNA, Satellite
  • Epigenesis, Genetic
  • Genetics
  • Glioblastoma
  • Humans
  • Molecular Biology
  • Neoplastic Stem Cells
  • Neurons
  • Stem cells

Fingerprint

Entra nei temi di ricerca di 'Loss of pericentromeric DNA methylation pattern in human glioblastoma is associated with altered DNA methyltransferases expression and involves the stem cell compartment'. Insieme formano una fingerprint unica.

Cita questo