Genetische Analyse maligner Gliome mittels Mikroarray-Technologie

Maligne Astrozytome des World Health Organization Grad III und IV haben eine stark reduzierte mediane Überlebenszeit. Zahlreiche möglichen molekularen Transduktionswege wurden bisher für die Progression des anaplastischen Astrozytoms zum Glioblastom beschrieben, jedoch ist die molekulare Basis der m...

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Bibliographic Details
Main Author: Köhler, Sylvia
Contributors: Bertalanffy, H. (Prof. Dr.) (Thesis advisor)
Format: Doctoral Thesis
Published: Philipps-Universität Marburg 2013
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Malignant astrocytomas of World Health Organization (WHO) grade III or IV are indicated by a significantly reduced median survival time. Several possible pathways have been described for the progression of anaplastic astrocytomas and glioblastomas, but the molecular basis of malignant astrocytoma progression has not been analysed entirely. Microarray analysis provides the chance to accelerate studies by comparison of thousands of genes in these tumours and consequently identify targeting genes and this might help to understand the malignant development. We compared the transcriptional profile of 4608 genes in tumours of 14 patients, including six (6) anaplastic astrocytomas (WHO grade III) and eight (8) glioblastomas (WHO grade IV) using microarray analysis. The microarray data should be validated by real-time reverse transcription-polymerase chain reaction analysis of 3 selected genes. A successful validation took place with gen RAB34. We identified 166 gene alterations with a fold change of 2 and higher whose mRNA levels differed considerably (absolute value of the t-statistic of 1.96) between the two malignant glioma groups. Further analyses confirmed oppositional transcription directions for OLIG2 and IL13RA2 in WHO grade III astrocytomas as compared to glioblastomas. Homogeneous results of both analyses were found on RAB34 In anaplastic astrocytomas and glioblastomas, which are histologically confirmed, microarray analyses with a closed binary question allow an identification of genes of different expression. RAB34, IL13RA2 and OLIG2 have been identified to be interesting candidate genes whose differential expression likely plays a role in malignant progression of astrocytomas.