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61. Jahrestagung der Deutschen Gesellschaft für Neurochirurgie (DGNC) im Rahmen der Neurowoche 2010
Joint Meeting mit der Brasilianischen Gesellschaft für Neurochirurgie am 20. September 2010

Deutsche Gesellschaft für Neurochirurgie (DGNC) e. V.

21. - 25.09.2010, Mannheim

A microarray-based DNA methylation analysis of brain metastases and their corresponding primary carcinomas

Meeting Abstract

  • Ramón Martínez - Klinik für Neurochirurgie der Universität Göttingen, Germany
  • Veit Rohde - Klinik für Neurochirurgie der Universität Göttingen, Germany
  • Angelika Gutenberg - Klinik für Neurochirurgie der Universität Göttingen, Germany
  • Laszlo Füzesi - Abteilung Gastroenteropathologie der Universität Göttingen, Germany
  • José Martín-Subero - Cancer Epigenetics and Biology Program, Bellvitge Biomedical Research Institute, Barcelona, Spain
  • Manel Esteller - Cancer Epigenetics and Biology Program, Bellvitge Biomedical Research Institute, Barcelona, Spain

Deutsche Gesellschaft für Neurochirurgie. 61. Jahrestagung der Deutschen Gesellschaft für Neurochirurgie (DGNC) im Rahmen der Neurowoche 2010. Mannheim, 21.-25.09.2010. Düsseldorf: German Medical Science GMS Publishing House; 2010. DocP1756

DOI: 10.3205/10dgnc227, URN: urn:nbn:de:0183-10dgnc2279

Veröffentlicht: 16. September 2010

© 2010 Martínez et al.
Dieser Artikel ist ein Open Access-Artikel und steht unter den Creative Commons Lizenzbedingungen (http://creativecommons.org/licenses/by-nc-nd/3.0/deed.de). Er darf vervielfältigt, verbreitet und öffentlich zugänglich gemacht werden, vorausgesetzt dass Autor und Quelle genannt werden.


Gliederung

Text

Objective: Aberrant gene methylation has been linked to metastasis through promoting mitotic recombination, deletions and chromosomal rearrangements. It leads to the repression of gene expression that enables tumor cells to metastasize or have a selective advantage at the secondary tissue site. The magnitude of DNA methylation in brain metastases is poorly devised. We have performed a microarray-based DNA methylation analysis of brain metastases and their corresponding renal- or colorectal primary carcinomas.

Methods: We analyzed brain metastases of 12 renal cell carcinomas and 15 cases of colorectal cancer and their corresponding primary carcinomas. The DNA methylation level of 1.505 CpG dinucleotides (807 genes) was quantified using universal BeadArrays with the Illumina GoldenGate Methylation Cancer Panel. Hierarchical clustering was performed on all tumors using the cluster analysis tool of the BeadStudio software. Methylation assay was performed as described (Bibikova et al, Genome Res 2006).

Results: Compared to the corresponding primary carcinomas, we have observed new hypermethylated CpGs (104 for renal cell carcinomas, 24 for colorectal carcinomas, in median) and new hypomethylated CpGs (74 for renal cell carcinomas, 43 for colorectal carcinomas, in median) in brain metastases. Genes undergoing aberrant hypermethylation in brain metastases included ADCYAP1, NTSR1, ERG, SLIT2 and POMC. Only NEU1 showed a new hypomethylation.

Conclusions:

1.
unsupervised analyses showed the presence of similar methylation patterns of brain metastases as compared to their corresponding primary carcinomas.
2.
different methylation signatures were evidenced in both primary cancers and brain metastases.
3.
supervised analyses reveal the existence of metastasis-associated genes that undergo differential hypermethylation or hypomethylation in brain metastases of renal cell and colorectal carcinomas.