Telomeraseaktivität beim Neuroblastom: prognostische Bedeutung in Abhängigkeit von MYCN-Amplifikation, Stadium, Alter bei Diagnose, Histologie und Geschlecht

Das Neuroblastom als Tumor des frühen Kindesalters imponiert durch eine außergewöhnliche biologische Heterogenität, die sich in sehr unterschiedlichen klinischen Verläufen äußert. Das Spektrum reicht von spontanen Regressionen bereits metastasierter Tumoren bis hin zu unaufhaltsamer Progression der...

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Bibliographic Details
Main Author: Schiel, Sibylle
Contributors: Christiansen, Holger (Prof. Dr.) (Thesis advisor)
Format: Dissertation
Language:German
Published: Philipps-Universität Marburg 2008
Zentrum für Kinder- und Jugendmedizin
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Table of Contents: Neuroblastoma as the second most common solid tumour in childhood shows an extraordinary biological heterogeneity ranging from spontaneous regression of metastatic tumours to rapid progression despite multimodal therapy. To determine the optimal treatment strategy for each individual patient with neuroblastoma, genetic factors play a decisive role in risk stratification. For two decades, amplification of the MYCN oncogene has been established as a clinical marker for unfavourable prognostic outcome. Recent reports suggest an important role also for telomerase in neuroblastomas. Telomerase is an enzyme that helps the cell to overcome its limited ability to proliferate. Since telomerase activity is absent in most non-neoplastic tissues and somatic cells but can be detected in almost all malignant tumours, it has potential as an diagnostic marker for malignancy. In this study we examined the prognostic importance of telomerase activity in neuroblastoma. In 304 tumours telomerase acitvity levels were determined using the telomeric repeat amplification protocol (TRAP). Genomic status of MYCN was quantified by PCR. Univariate and multivariate analyses were performed for telomerase activity, amplification status of MYCN, the variables tumour stage, age at first biopsy, histopathological grading and gender. This study could demonstrate in a large series of neuroblastomas that elevated levels of telomerase activity are associated with poor prognosis independently of known clinical parameters as tumour stage, age at diagnosis, histopathological grading and amplification of the oncogene MYCN. In addition, both amplification of MYCN and tumour stage 4 were affirmed as independent prognostic factors in neuroblastoma.