Analysis of <i>HIC‐1</i> methylation and transcription in human ependymomas

Waha, Anke; Koch, Arend; Hartmann, Wolfgang; Mack, Heike Heike; Schramm, Johannes; Sörensen, N.; Berthold, Frank; Wiestler, Otmar D.; Pietsch, Torsten; Waha, Andreas

doi:10.1002/ijc.20165

Cited by 65 publications

(35 citation statements)

References 40 publications

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“…However, in contrast to a recent report by Chen et al (2003), we did not observe a female predominance among HIC1 heterozygous DLBCL patients. Since, HIC1 has been reported to be frequently inactivated by hypermethylation in hematological malignancies (Issa et al, 1997;Melki et al, 1999) as well as in solid tumors (Kanai et al, 1999;Dong et al, 2001;Rathi et al, 2003;Waha et al, 2004), we focused our investigation on this gene, in particular its inactivation by methylation. According to the results of our study, several lines of evidence suggest a putative tumor suppressor role for HIC1 in DLBCL.…”

Section: Discussionmentioning

confidence: 99%

Detailed mapping of chromosome 17p deletions reveals HIC1 as a novel tumor suppressor gene candidate telomeric to TP53 in diffuse large B-cell lymphoma

et al. 2007

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Deletions in the short arm of chromosome 17 (17p) involving the tumor suppressor TP53 occur in up to 20% of diffuse large B-cell lymphomas (DLBCLs). Although inactivation of both alleles of a tumor suppressor gene is usually required for tumor development, the overlap between TP53 deletions and mutations is poorly understood in DLBCLs, suggesting the possible existence of additional tumor suppressor genes in 17p. Using a bacterial artificial chromosome (BAC) and Phage 1 artificial chromosome (PAC) contig, we here define a minimally deleted region in DLBCLs encompassing approximately 0.8 MB telomeric to the TP53 locus. This genomic region harbors the tumor suppressor Hypermethylated in Cancer 1 (HIC1). Methylation-specific PCR demonstrated hypermethylation of HIC1 exon 1a in a substantial subset of DLBCLs, which is accompanied by simultaneous HIC1 deletion of the second allele in 90% of cases. In contrast, HIC1 inactivation by hypermethylation was rarely encountered in DLBCLs without concomitant loss of the second allele. DLBCL patients with complete inactivation of both HIC1 and TP53 may be characterized by an even inferior clinical course than patients with inactivation of TP53 alone, suggesting a functional cooperation between these two proteins. These findings strongly imply HIC1 as a novel tumor suppressor in a subset of DLBCLs.

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Section: Discussionmentioning

confidence: 99%

Detailed mapping of chromosome 17p deletions reveals HIC1 as a novel tumor suppressor gene candidate telomeric to TP53 in diffuse large B-cell lymphoma

et al. 2007

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“…4C), and a relatively high degree of epigenetic silencing of the 17p tumor suppressor gene HIC-1 by promoter DNA methylation (87). At recurrence, the loss of chromosome 6q seems exclusive to posterior fossa tumors, as determined by CGH (Fig.…”

Section: Ependymoma Heterogeneity and Tumor Locationmentioning

confidence: 92%

Pediatric Ependymoma: Biological Perspectives

Kilday

Rahman

Dyer

et al. 2009

Molecular Cancer Research

168

204

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Pediatric ependymomas are enigmatic tumors that continue to present a clinical management challenge despite advances in neurosurgery, neuroimaging techniques, and radiation therapy. Difficulty in predicting tumor behavior from clinical and histological factors has shifted the focus to the molecular and cellular biology of ependymoma in order to identify new correlates of disease outcome and novel therapeutic targets. This article reviews our current understanding of pediatric ependymoma biology and includes a meta-analysis of all comparative genomic hybridization (CGH) studies done on primary ependymomas to date, examining more than 300 tumors. From this meta-analysis and a review of the literature, we show that ependymomas in children exhibit a different genomic profile to those in adults and reinforce the evidence that ependymomas from different locations within the central nervous system (CNS) are distinguishable at a genomic level. Potential biological markers of prognosis in pediatric ependymoma are assessed and the ependymoma cancer stem cell hypothesis is highlighted with respect to tumor resistance and recurrence. We also discuss the shifting paradigm for treatment modalities in ependymoma that target molecular alterations in tumor-initiating cell populations. (Mol Cancer Res 2009;7(6):765-86)

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“…2 The putative tumor repressor gene HIC1, also epigenetically silenced in medulloblastomas, was hypermethylated in 83% of ependymomas that primarily had a nonspinal localization. 150 The most commonly methylated tumor suppressor gene in ependymoma was RASSF1A (86%) regardless of clinical or pathological subtype. 57 Other frequently methylated genes in ependymoma include MCJ, FHIT, RARB, BLU, p16INK4a, DAPK, and TRAIL pathway-related genes (CASP8, TFRS-F10C, and TFRSF10D).…”

Section: Ependymomamentioning

confidence: 99%

Epigenetic mechanisms regulating neural development and pediatric brain tumor formation

Faria

Rutka

Smith

et al. 2011

PED

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Pediatric brain tumors are the leading cause of cancer-related death in children, and among them, embryonal tumors represent the largest group with an associated poor prognosis and long-term morbidity for survivors. The field of cancer epigenetics has emerged recently as an important area of investigation and causation of a variety of neoplasms, and is defined as alterations in gene expression without changes in DNA sequence. The best studied epigenetic modifications are DNA methylation, histone modifications, and RNA-based mechanisms. These modifications play an important role in normal development and differentiation but their dysregulation can lead to altered gene function and cancer. In this review the authors describe the mechanisms of normal epigenetic regulation, how they interplay in neuroembryogenesis, and how these can cause brain tumors in children when dysregulated. The potential use of epigenetic markers to design more effective treatment strategies for children with malignant brain tumors is also discussed.

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Analysis of HIC‐1 methylation and transcription in human ependymomas

Cited by 65 publications

References 40 publications

Detailed mapping of chromosome 17p deletions reveals HIC1 as a novel tumor suppressor gene candidate telomeric to TP53 in diffuse large B-cell lymphoma

Detailed mapping of chromosome 17p deletions reveals HIC1 as a novel tumor suppressor gene candidate telomeric to TP53 in diffuse large B-cell lymphoma

Pediatric Ependymoma: Biological Perspectives

Epigenetic mechanisms regulating neural development and pediatric brain tumor formation

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