Journal ArticleDOI
High promoter hypermethylation frequency of p14/ARF in supratentorial PNET but not in medulloblastoma.
M. M. Inda,J Muñoz,Philippe Coullin,Didier Fauvet,G. Danglot,T Tuñón,Alain Bernheim,J S Castresana +7 more
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TLDR
The aim of this study was to determine whether sPNET and MB are genetically different entities, and if so, what characteristics make them different.Abstract:
Aims : Medulloblastoma (MB) is the most common primitive neuroectodermal tumour (PNET) of the central nervous system. Although supratentorial PNET (sPNET) and MB are histologically similar, their clinical behaviour differs, sPNET being more aggressive than MB. The aim of this study was to determine whether sPNET and MB are genetically different entities.
Methods and results : We investigated 32 PNET primary tumour samples (23 MB and nine sPNET) and four PNET cell lines, for the presence of CDKN2A homozygous deletions at exon 1-α of p16/INK4 and exon 1-β of p14/ARF, and promoter hypermethylation of both genes. No homozygous deletion of either p16/INK4 or p14/ARF was demonstrated in any of the PNET primary tumour samples. Methylation of p16/INK4 was found in one of six sPNET and in one of 23 MB, while p14/ARF methylation was observed in three of six sPNET and in three of 21 MB. No methylation of p16/INK4 or p14/ARF was found in any of the PNET cell lines analysed. The three MB cell lines did not show p16/INK4 expression, and only the MB Daoy cell line (homozygously deleted at CDKN2A) presented loss of p14/ARF expression.
Conclusions : Our results in this limited series of central PNET show that p14/ARF is frequently involved in PNET carcinogenesis, with a higher frequency, but not statistically significant, for sPNET than for MB.read more
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Journal ArticleDOI
Epigenetic principles and mechanisms underlying nervous system functions in health and disease.
TL;DR: Pharmacoepigenomic therapies will promote accelerated recovery of impaired and seemingly irrevocably lost cognitive, behavioral, sensorimotor functions through epigenetic reprogramming of endogenous regional neural stem cell fate decisions, targeted tissue remodeling and restoration of neural network integrity, plasticity and connectivity.
Journal ArticleDOI
Contribution of polycomb homologues Bmi-1 and Mel-18 to medulloblastoma pathogenesis.
Dmitri Wiederschain,Lin Chen,Brett V. Johnson,Kimberly Bettano,Dowdy Jackson,John A. Taraszka,Y. Karen Wang,Michael D. Jones,Michael Morrissey,James Deeds,Rebecca Mosher,Paul Fordjour,Christoph Lengauer,John D. Benson +13 more
TL;DR: It is reported here that short hairpin RNA-mediated knockdown of either Bmi-1 or Mel-18 in human medulloblastoma DAOY cells results in the inhibition of proliferation, loss of clonogenic survival, anchorage-independent growth, and suppression of tumor formation in nude mice.
Journal ArticleDOI
Supratentorial primitive neuroectodermal tumors of the central nervous system frequently harbor deletions of the CDKN2A locus and other genomic aberrations distinct from medulloblastomas
Stefan M. Pfister,Stefan M. Pfister,Marc Remke,Grischa Toedt,Wiebke Werft,Axel Benner,Frank Mendrzyk,Andrea Wittmann,Frauke Devens,Katja von Hoff,Stefan Rutkowski,Andreas E. Kulozik,Bernhard Radlwimmer,Wolfram Scheurlen,Peter Lichter,Andrey Korshunov +15 more
TL;DR: Differences in the frequency of copy‐number losses at chromosome regions 1p12‐22.1 and 9p, and gains at 19p, all of them more frequently occurring in stPNETs are identified, which support the hypothesis of two different tumor entities of embryonal neuroepithelial tumors with characteristic genetic aberrations.
Journal ArticleDOI
Genome-wide molecular characterization of central nervous system primitive neuroectodermal tumor and pineoblastoma
Suzanne Miller,Hazel A. Rogers,Paul C. Lyon,Vikki Rand,Martyna Adamowicz-Brice,Steven C. Clifford,James Hayden,Sara Dyer,Stefan M. Pfister,Andrey Korshunov,Marie-Anne Brundler,James Lowe,Beth Coyle,Richard Grundy +13 more
TL;DR: This genome-wide analysis revealed the marked molecular heterogeneity of CNS PNETs and enabled the identification of novel genes and clinical associations potentially involved in the pathogenesis of these tumors.
Journal ArticleDOI
The Genetics of Pediatric Brain Tumors
Adrian M. Dubuc,Adrian M. Dubuc,Paul A. Northcott,Paul A. Northcott,Stephen C. Mack,Stephen C. Mack,Hendrik Witt,Hendrik Witt,Stefan M. Pfister,Stefan M. Pfister,Michael D. Taylor,Michael D. Taylor +11 more
TL;DR: This review summarizes the current state of knowledge, emphasizes recent seminal findings in the field, and proposes future research efforts needed to further characterize the genetic basis of pediatric brain tumors.
References
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Journal ArticleDOI
Methylation-specific PCR: a novel PCR assay for methylation status of CpG islands
TL;DR: The use of MSP is demonstrated to identify promoter region hypermethylation changes associated with transcriptional inactivation in four important tumor suppressor genes (p16, p15, E-cadherin and von Hippel-Lindau) in human cancer.
Journal ArticleDOI
The alternative product from the human CDKN2A locus, p14ARF, participates in a regulatory feedback loop with p53 and MDM2
Francesca J. Stott,Stewart Bates,Marion C. James,Beth B. McConnell,Maria Starborg,Sharon Brookes,Ignacio Palmero,Ignacio Palmero,Kevin M. Ryan,Eiji Hara,Karen H. Vousden,Gordon Peters +11 more
TL;DR: The results place p14ARF in an independent pathway upstream of p53 and imply that CDKN2A encodes two proteins that are involved in tumour suppression.
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Pathology and Genetics of Tumours of the Nervous System
TL;DR: The new edition of this publication opens with the recently revised WHO Classification of Tumors of the Nervous System and then systematically presents each of these tumors and familial tumor syndromes in a …
Journal ArticleDOI
Pathology and Genetics of Tumours of the Nervous System
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Journal ArticleDOI
DMBT1, a new member of the SRCR superfamily, on chromosome 10q25.3-26.1 is deleted in malignant brain tumours
Jan Mollenhauer,Stefan Wiemann,Wolfram Scheurlen,Bernhard Korn,Yutaka Hayashi,Klaus K. Wilgenbus,Andreas von Deimling,Annemarie Poustka +7 more
TL;DR: It is suggested that DMBT1 is a putative tumour-suppressor gene implicated in the carcinogenesis of medulloblastoma and glioblastomas multiforme.
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