DNA methylation and allelic losses on chromosome arm 14q in oligodendroglial tumours

J. Felsberg, P. S. Yan, Hui-ming Huang, U. Milde, J. Schramm, O. D. Wiestler, G. Reifenberger, T. Pietsch, A. Waha

Research output: Contribution to journalArticle

21 Citations (Scopus)

Abstract

Cytogenetic and molecular genetic studies have shown frequent losses on the long arm of chromosome 14 in different types of human gliomas. Using differential methylation hybridization as a genome-wide screening approach to determine DNA methylation patterns in gliomas, we recently identified two DNA fragments in 14q23.1 (CGI-clone #396) and 14q32.12 (CGI-clone #519) that were differentially methylated between astrocytic gliomas and mixed oligoastrocytomas. To validate this observation, we examined these 14q32.12 locus for methylation in an extended series of 43 astrocytic and oligodendroglial gliomas. All tumours were additionally investigated for loss of heterozygosity (LOH). Microsatellite analysis showed LOH in seven of 28 (25%) oligodendroglial tumours and three of 15 (20%) astrocytic tumours. Seven tumours demonstrated LOH at all informative 14q loci whereas three tumours carried partial deletions defining a commonly deleted region at 14q22.3-q32.1 between the microsatellite markers D14S282 and D14S995. Methylation-specific PCR analysis of the 14q32.12 locus revealed hypermethylation in 12 of 43 gliomas (28%). Hypermethylation was restricted to tumours with oligodendroglial differentiation (12 of 28 tumours, 43%). However, none of the hypermethylated tumours demonstrated LOH on 14q and vice versa. In total, 19 of 28 oligodendroglial tumours (68%) showed either hypermethylation at the 14q32.12 locus or LOH at 14q22.3-q32.2. Taken together, our data lend further support for the location of one or more yet to be identified glioma-associated tumour suppressor gene(s) on 14q. In addition, the restriction of 14q32.12 methylation to oligodendroglial tumours suggests a role for epigenetic DNA modifications in these particular gliomas.

Original languageEnglish (US)
Pages (from-to)517-524
Number of pages8
JournalNeuropathology and Applied Neurobiology
Volume32
Issue number5
DOIs
StatePublished - Oct 2006
Externally publishedYes

Fingerprint

Loss of Heterozygosity
DNA Methylation
Chromosomes
Glioma
Neoplasms
Methylation
Astrocytoma
Microsatellite Repeats
Clone Cells
Chromosomes, Human, Pair 14
DNA
Tumor Suppressor Genes
Epigenomics
Cytogenetics
Molecular Biology
Genome
Polymerase Chain Reaction

Keywords

  • Chromosome 14
  • DNA methylation
  • Loss of heterozygosity
  • Oligodendroglioma
  • Tumour suppressor gene

ASJC Scopus subject areas

  • Clinical Neurology
  • Pathology and Forensic Medicine
  • Neuroscience(all)

Cite this

DNA methylation and allelic losses on chromosome arm 14q in oligodendroglial tumours. / Felsberg, J.; Yan, P. S.; Huang, Hui-ming; Milde, U.; Schramm, J.; Wiestler, O. D.; Reifenberger, G.; Pietsch, T.; Waha, A.

In: Neuropathology and Applied Neurobiology, Vol. 32, No. 5, 10.2006, p. 517-524.

Research output: Contribution to journalArticle

Felsberg, J, Yan, PS, Huang, H, Milde, U, Schramm, J, Wiestler, OD, Reifenberger, G, Pietsch, T & Waha, A 2006, 'DNA methylation and allelic losses on chromosome arm 14q in oligodendroglial tumours', Neuropathology and Applied Neurobiology, vol. 32, no. 5, pp. 517-524. https://doi.org/10.1111/j.1365-2990.2006.00759.x
Felsberg, J. ; Yan, P. S. ; Huang, Hui-ming ; Milde, U. ; Schramm, J. ; Wiestler, O. D. ; Reifenberger, G. ; Pietsch, T. ; Waha, A. / DNA methylation and allelic losses on chromosome arm 14q in oligodendroglial tumours. In: Neuropathology and Applied Neurobiology. 2006 ; Vol. 32, No. 5. pp. 517-524.
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abstract = "Cytogenetic and molecular genetic studies have shown frequent losses on the long arm of chromosome 14 in different types of human gliomas. Using differential methylation hybridization as a genome-wide screening approach to determine DNA methylation patterns in gliomas, we recently identified two DNA fragments in 14q23.1 (CGI-clone #396) and 14q32.12 (CGI-clone #519) that were differentially methylated between astrocytic gliomas and mixed oligoastrocytomas. To validate this observation, we examined these 14q32.12 locus for methylation in an extended series of 43 astrocytic and oligodendroglial gliomas. All tumours were additionally investigated for loss of heterozygosity (LOH). Microsatellite analysis showed LOH in seven of 28 (25{\%}) oligodendroglial tumours and three of 15 (20{\%}) astrocytic tumours. Seven tumours demonstrated LOH at all informative 14q loci whereas three tumours carried partial deletions defining a commonly deleted region at 14q22.3-q32.1 between the microsatellite markers D14S282 and D14S995. Methylation-specific PCR analysis of the 14q32.12 locus revealed hypermethylation in 12 of 43 gliomas (28{\%}). Hypermethylation was restricted to tumours with oligodendroglial differentiation (12 of 28 tumours, 43{\%}). However, none of the hypermethylated tumours demonstrated LOH on 14q and vice versa. In total, 19 of 28 oligodendroglial tumours (68{\%}) showed either hypermethylation at the 14q32.12 locus or LOH at 14q22.3-q32.2. Taken together, our data lend further support for the location of one or more yet to be identified glioma-associated tumour suppressor gene(s) on 14q. In addition, the restriction of 14q32.12 methylation to oligodendroglial tumours suggests a role for epigenetic DNA modifications in these particular gliomas.",
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AU - Yan, P. S.

AU - Huang, Hui-ming

AU - Milde, U.

AU - Schramm, J.

AU - Wiestler, O. D.

AU - Reifenberger, G.

AU - Pietsch, T.

AU - Waha, A.

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N2 - Cytogenetic and molecular genetic studies have shown frequent losses on the long arm of chromosome 14 in different types of human gliomas. Using differential methylation hybridization as a genome-wide screening approach to determine DNA methylation patterns in gliomas, we recently identified two DNA fragments in 14q23.1 (CGI-clone #396) and 14q32.12 (CGI-clone #519) that were differentially methylated between astrocytic gliomas and mixed oligoastrocytomas. To validate this observation, we examined these 14q32.12 locus for methylation in an extended series of 43 astrocytic and oligodendroglial gliomas. All tumours were additionally investigated for loss of heterozygosity (LOH). Microsatellite analysis showed LOH in seven of 28 (25%) oligodendroglial tumours and three of 15 (20%) astrocytic tumours. Seven tumours demonstrated LOH at all informative 14q loci whereas three tumours carried partial deletions defining a commonly deleted region at 14q22.3-q32.1 between the microsatellite markers D14S282 and D14S995. Methylation-specific PCR analysis of the 14q32.12 locus revealed hypermethylation in 12 of 43 gliomas (28%). Hypermethylation was restricted to tumours with oligodendroglial differentiation (12 of 28 tumours, 43%). However, none of the hypermethylated tumours demonstrated LOH on 14q and vice versa. In total, 19 of 28 oligodendroglial tumours (68%) showed either hypermethylation at the 14q32.12 locus or LOH at 14q22.3-q32.2. Taken together, our data lend further support for the location of one or more yet to be identified glioma-associated tumour suppressor gene(s) on 14q. In addition, the restriction of 14q32.12 methylation to oligodendroglial tumours suggests a role for epigenetic DNA modifications in these particular gliomas.

AB - Cytogenetic and molecular genetic studies have shown frequent losses on the long arm of chromosome 14 in different types of human gliomas. Using differential methylation hybridization as a genome-wide screening approach to determine DNA methylation patterns in gliomas, we recently identified two DNA fragments in 14q23.1 (CGI-clone #396) and 14q32.12 (CGI-clone #519) that were differentially methylated between astrocytic gliomas and mixed oligoastrocytomas. To validate this observation, we examined these 14q32.12 locus for methylation in an extended series of 43 astrocytic and oligodendroglial gliomas. All tumours were additionally investigated for loss of heterozygosity (LOH). Microsatellite analysis showed LOH in seven of 28 (25%) oligodendroglial tumours and three of 15 (20%) astrocytic tumours. Seven tumours demonstrated LOH at all informative 14q loci whereas three tumours carried partial deletions defining a commonly deleted region at 14q22.3-q32.1 between the microsatellite markers D14S282 and D14S995. Methylation-specific PCR analysis of the 14q32.12 locus revealed hypermethylation in 12 of 43 gliomas (28%). Hypermethylation was restricted to tumours with oligodendroglial differentiation (12 of 28 tumours, 43%). However, none of the hypermethylated tumours demonstrated LOH on 14q and vice versa. In total, 19 of 28 oligodendroglial tumours (68%) showed either hypermethylation at the 14q32.12 locus or LOH at 14q22.3-q32.2. Taken together, our data lend further support for the location of one or more yet to be identified glioma-associated tumour suppressor gene(s) on 14q. In addition, the restriction of 14q32.12 methylation to oligodendroglial tumours suggests a role for epigenetic DNA modifications in these particular gliomas.

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