Abstracts (poster) - Wissenschaft Online

Michael Grzendowski, Markus J. Riemenschneider, Marietta Wolter, Uwe Schlegel,
Helmut E. Meyer, Guido Reifenberger, Kai Stühler
Proteome analysis of human glioma with 1p/19q LOH
Gliomas, the most common primary brain tumors, are histologically classified on the
basis of morphological and immunohistochemical features as defined in the World Health
Organization (WHO) classification of tumors of the nervous system. In addition to the
histological assessment, certain genetic factors, such as allelic losses on chromosome
arms 1p and 19q, are able to provide clinically useful information that may help to
stratify gliomas into prognostically distinct subgroups. In particular, recent randomized
trials have strongly associated 1p/19q-deletion with response to radio- and
chemotherapy as well as longer survival in patients with anaplastic oligodendrogliomas
and anaplastic oligoastrocytomas (Cairncross et al., J. Clin. Oncol. 24, 2707-14, 2006;
van den Bent et al., J. Clin. Oncol. 24, 2715-22, 2006).
To identify proteins that are differentially expressed between gliomas with and without
1p/19q-deletion, we performed a proteomic analysis on oligoastrocytomas using
differential gel electrophoresis (DIGE) followed by MALDI-TOF/TOF mass spectrometry.
Thereby, we identified 46 differentially expressed proteins (• ≥ 1.8, p ≤ 0.05). From
these candidate proteins we selected the first promising proteins for further analysis and
confirmed the differential expression of four candidate proteins by using Western-blot
analysis and immunohistochemistry. Subsequent epigenetic analysis revealed promoter
hypermethylation as the major cause for low mRNA and protein expression levels of
these four candidates in oligodendroglial tumors with 1p/19q loss. Further clinical
validation of these differentially expressed proteins on larger patient cohorts is ongoing
to assess their utility as potential biomarkers for classification and prognostic
assessment. This overall approach provides a powerful means to identify proteome wide
alterations associated with allelic status on 1p/19q and thus may help in identifying
novel, highly relevant prognostic glioma markers.
contact:
Michael Grzendowski
Ruhr-Universität Bochum
Medizinisches Proteom-Center
michael.grzendowski@rub.de
Universitätsstr.150
44801 Bochum (Germany)