gms | German Medical Science

58. Jahrestagung der Deutschen Gesellschaft für Neurochirurgie e. V. (DGNC)

Deutsche Gesellschaft für Neurochirurgie (DGNC) e. V.

26. bis 29.04.2007, Leipzig

Study of PTEN methylation in 69 cases of cerebral cavernous malformations (CCMs). Possible impact on familial cases

PTEN-Methylierung in 69 Fällen von zerebralen Kavernomen. Möglicher Einfluss auf familiäre Fälle

Meeting Abstract

  • corresponding author Y. Zhu - Klinik für Neurochirurgie, Universitätsklinikum Gießen und Marburg, Standort Marburg
  • A. Wloch - Klinik für Neurochirurgie, Universitätsklinikum Gießen und Marburg, Standort Marburg
  • H. X. An - Klinik für Strahlentherapie, Universitätsklinikum Gießen und Marburg, Standort Marburg
  • M. Hallier-Nelsen - Klinik für Neurochirurgie, Universitätsklinikum Gießen und Marburg, Standort Marburg
  • T. Mikami - Klinik für Neurochirurgie, Universitätsklinikum Gießen und Marburg, Standort Marburg
  • R. Engenhart-Cabillic - Klinik für Strahlentherapie, Universitätsklinikum Gießen und Marburg, Standort Marburg
  • H. Bertalanffy - Klinik für Neurochirurgie, Universitätsklinikum Gießen und Marburg, Standort Marburg
  • U. Sure - Klinik für Neurochirurgie, Universitätsklinikum Gießen und Marburg, Standort Marburg

Deutsche Gesellschaft für Neurochirurgie. 58. Jahrestagung der Deutschen Gesellschaft für Neurochirurgie e.V. (DGNC). Leipzig, 26.-29.04.2007. Düsseldorf: German Medical Science GMS Publishing House; 2007. DocP 070

The electronic version of this article is the complete one and can be found online at: http://www.egms.de/en/meetings/dgnc2007/07dgnc325.shtml

Published: April 11, 2007

© 2007 Zhu et al.
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Outline

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Objective: We and others have demonstrated that CCM is a dynamically developing disease involving neoangiogenesis. Our rescent study has revealed a significant loss of PTEN in the cerebral vessels of CCM and furthermore a crucial role of PTEN in angiogenesis. Frequent PTEN deficiency due to promoter hypermethylation has been reported in various cancers. It is highly interesting to explore whether PTEN methylation occurs in CCM patients and whether this epigenic mutation accounts for PTEN loss in CCM patients.

Methods: To study PTEN methylation, genomic DNA was extracted from 69 CCM brain tissues and 4 blood cell samples from familial CCMs (f-CCMs). DNA was modified by sodium bisulfite followed by methylation specific PCR (MSP). A positive control was prepared using the genomic DNA from healthy human blood that was treated with SssI methylase. To find out the correlation of PTEN expression and methylation, immunostaining of PTEN was performed.

Results: MSP revealed PTEN methylation positive with 10 among 69 brain tissues of CCMs (14.5%). Interestingly, all 4 f-CCMs showed PTEN methylation positive. The incidence of PTEN methylation in f-CCMs (100%) is significantly higher than the sporadic one (9.2%) (p<0.001). Of note, only 1 among 4 cases of f-CCMs showed PTEN methylation positive both in blood cells and in surgical tissues, whereas other 3 cases showed negative in blood cell sample indicating a tissue-specific PTEN methylation in these cases. Immunostaining demonstrated a significant higher PTEN loss in PTEN methylation positive cases (67%) in comparison to that in methylation negative CCMs (29%) (p<0.001).

Conclusions: The present study reports for the first time that PTEN methylation is present in the lesioned brain tissue of CCM patients, particularly in f-CCMs, suggesting a possible novel diagnosis parameter among others for f-CCMs.