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Nucleic Acids Research Advance Access originally published online on March 7, 2007
Nucleic Acids Research 2007 35(7):e51; doi:10.1093/nar/gkm094
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Nucleic Acids Research, 2007, Vol. 35, No. 7 e51
© 2007 The Author(s)
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/2.0/uk/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

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Array-based profiling of reference-independent methylation status (aPRIMES) identifies frequent promoter methylation and consecutive downregulation of ZIC2 in pediatric medulloblastoma

Stefan Pfister1,2, Christof Schlaeger1, Frank Mendrzyk1, Andrea Wittmann1, Axel Benner3, Andreas Kulozik2, Wolfram Scheurlen4, Bernhard Radlwimmer1 and Peter Lichter1,*

1Department of Molecular Genetics, German Cancer Research Center, Im Neuenheimer Feld 280, 69120 Heidelberg, Germany, 2Department of Pediatric Oncology, Hematology & Immunology, University of Heidelberg, Im Neuenheimer Feld 153, 69120 Heidelberg, Germany, 3Central Unit Biostatistics, German Cancer Research Center, Im Neuenheimer Feld 280, 69120 Heidelberg, Germany and 4Cnopf'sche Kinderklinik, Nürnberg Children's Hospital, St. Johannis Muehlgasse 19, 90419 Nuernberg, Germany

*To whom correspondence should be addressed. Tel: +49-6221-424619; Fax: +49-6221-424639; Email: m.macleod{at}dkfz.de

Received October 16, 2006. Revised February 1, 2007. Accepted February 2, 2007.

Existing microarray-based approaches for screening of DNA methylation are hampered by a number of shortcomings, such as the introduction of bias by DNA copy-number imbalances in the test genome and negligence of tissue-specific methylation patterns. We developed a method designated array-based profiling of reference-independent methylation status (aPRIMES) that allows the detection of direct methylation status rather than relative methylation. Array-PRIMES is based on the differential restriction and competitive hybridization of methylated and unmethylated DNA by methylation-specific and methylation-sensitive restriction enzymes, respectively. We demonstrate the accuracy of aPRIMES in detecting the methylation status of CpG islands for different states of methylation. Application of aPRIMES to the DNA from desmoplastic medulloblastomas of monozygotic twins showed strikingly similar methylation profiles. Additional analysis of 18 sporadic medulloblastomas revealed an overall correlation between highly methylated tumors and poor clinical outcome and identified ZIC2 as a frequently methylated gene in pediatric medulloblastoma.

The authors wish it to be known that, in their opinion, the first two authors should be regarded as joint First Authors


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C. Bock, J. Walter, M. Paulsen, and T. Lengauer
Inter-individual variation of DNA methylation and its implications for large-scale epigenome mapping
Nucleic Acids Res., June 1, 2008; 36(10): e55 - e55.
[Abstract] [Full Text] [PDF]


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