Aberrant hypermethylation of the major breakpoint cluster region in 17p11.2 in medulloblastomas but not supratentorial PNETs

Frühwald, Michael C.; O’Dorisio, M. Sue; Dai, Zunyan; Rush, Laura J.; Krahe, Ralf; Smiraglia, Dominic J.; Pietsch, Torsten; Elsea, Sarah H.; Plass, Christoph

doi:10.1002/1098-2264(2000)9999:9999<::aid-gcc1052>3.0.co;2-s

Cited by 56 publications

(33 citation statements)

References 37 publications

(48 reference statements)

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“…cDNA was tested and normalized by amplification of GPI. Primers as published (Fru¨hwald et al, 2000;Teitz et al, 2000;Burbee et al, 2001). cDNA (1 ml) was added to 0.4 mM of each primer, 0.4 mM dNTPs, 4% DMSO, 2 mM MgCl 2 and 1.25 U Platinum Taq in 25 ml of buffer (200 mM Tris-HCl pH 8.4 500 mM KCl, Invitrogen, Karlsruhe).…”

supporting

confidence: 92%

“…In previous biological, clinical and epidemiological studies sPNET and AT/RT have mostly been coanalysed with MB. While AT/RT and sPNET share histopathological features with MB they clearly differ on a molecular level (Biegel et al, 1992;Russo et al, 1999;Fru¨hwald et al, 2001a). In this study, we collected tissue samples of two large German centers (Muenster and Wuerzburg) derived from 24 sPNET and six AT/RT and evaluated aberrant methylation of RASSF1A and CASP8 and the potential consequences on gene expression.…”

Section: Reportmentioning

confidence: 99%

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Epigenetic repression of RASSF1A but not CASP8 in supratentorial PNET (sPNET) and atypical teratoid/rhabdoid tumors (AT/RT) of childhood

et al. 2005

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Supratentorial primitive neuroectodermal tumors (sPNET) and atypical teratoid/rhabdoid tumors (AT/RT) of the CNS represent a biological and clinical enigma, despite advances in both molecular techniques and clinical management for these two rare embryonal brain tumors of childhood. Epigenetic changes hold great potential as possible disease mechanisms and may be manipulated therapeutically. We thus studied aberrant methylation of the genes RASSF1A and CASP8 and its consequence on expression in cell lines and primary tumors using a combination of semiquantitative methylation specific PCR (MSP), bisulfite sequencing and RT-PCR. In all, 17 samples of autopsy-derived normal appearing brain served as controls. Opposed to control tissues 19/24 sPNET and 4/6 AT/RT demonstrated aberrant methylation for the RASSF1A promoter region. Treatment of cell lines using 5-Aza-2 0 -deoxycytidine (5AZA) alone or in combination with trichostatin A (TSA) succeeded in re-establishing expression of RASSF1A in cell lines derived from a renal rhabdoid, an AT/RT and a medulloblastoma. A 5 0 CpG-rich region of CASP8 was methylated in normal tissues and in tumors. However, CASP8 showed inconsistent expression patterns in normal and tumor tissues. Our results indicate that aberrant methylation of the RASSF1A promoter region may be of importance in the origin and progression of sPNET and AT/ RT while the analysed 5 0 -CpG rich region of the CASP8 gene does not seem to play an important role in these tumors. Further studies of epigenetic changes in these rare tumors are warranted as their biology remains obscure and treatment efforts have been rather unsuccessfull.

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supporting

confidence: 92%

Section: Reportmentioning

confidence: 99%

Epigenetic repression of RASSF1A but not CASP8 in supratentorial PNET (sPNET) and atypical teratoid/rhabdoid tumors (AT/RT) of childhood

et al. 2005

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“…Such findings have expanded Knudson's 2-hit hypothesis to include epigenetic mechanisms of gene silencing [29]. Systematic analysis of specific genes and global methylation has demonstrated that methylation patterns differ between MBs and SPNETs [30,31]. Herein we have presented our evaluation of the role of genetic and epigenetic changes on gene expression of DLC-1, by which gene silencing is related to various types of human cancers, in MBs and SPNETs.…”

Section: Discussionmentioning

confidence: 99%

Epigenetic inactivation of DLC-1 in supratentorial primitive neuroectodermal tumor

et al. 2005

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“…There are deletions of chromosome 17p in as many as 50% of medulloblastomas [12]. Lost chromosomal regions, identified as deleted in malignant brain tumors (DMBT1), have been identified on 10q, 11p, and 16q [13].…”

Section: Geneticsmentioning

confidence: 84%

Primitive neuroectodermal tumors/medulloblastoma

M¹

2002

Curr Neurol Neurosci Rep

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The therapy for medulloblastoma/primitive neuroectodermal tumors of the central nervous system is surgery, followed by combination chemo-radiotherapy. The radiation field is the entire craniospinal axis, which is only avoided when treating infants. The treatment is, therefore, lengthy and toxic. Less aggressive therapy is given to patients who clinically appear to have less evidence of disease. Intensive basic research has begun to identify genetic factors of the disease, but these remain far from clinical application.

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Aberrant hypermethylation of the major breakpoint cluster region in 17p11.2 in medulloblastomas but not supratentorial PNETs

Cited by 56 publications

References 37 publications

Epigenetic repression of RASSF1A but not CASP8 in supratentorial PNET (sPNET) and atypical teratoid/rhabdoid tumors (AT/RT) of childhood

Epigenetic repression of RASSF1A but not CASP8 in supratentorial PNET (sPNET) and atypical teratoid/rhabdoid tumors (AT/RT) of childhood

Epigenetic inactivation of DLC-1 in supratentorial primitive neuroectodermal tumor

Primitive neuroectodermal tumors/medulloblastoma

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