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DOI: 10.1055/s-2008-1065345
© Georg Thieme Verlag KG Stuttgart · New York
Risk Estimation of Neuroblastoma Patients Using Molecular Markers
Die Bedeutung molekularer Marker für die Risikoabschätzung bei Neuroblastom-PatientenPublication History
Publication Date:
13 May 2008 (online)
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Abstract
The pediatric tumor neuroblastoma is a heterogeneous disease: Patients’ clinical courses can range from spontaneous regression to fatal progression of the disease. Accordingly, treatment protocols vary from “wait and see” approaches to intensive multimodal therapies. Accurate risk estimation of the patients is therefore mandatory to choose the most adequate therapy. Current trials stratify by a limited number of clinical variables, such as stage of the disease and age of the patient at diagnosis, as well as molecular markers, such as amplification of the oncogene MYCN and loss of the short arm of chromosome 1. However, misclassifications of patients still occur, and thus, a precise prediction of the clinical courses remains a challenge of neuroblastoma research. In recent years, genomic alterations and gene expression profiles of this neoplasm have been characterized thoroughly. It has been shown that the diverse clinical phenotypes are reflected by both specific cytogenetic aberrations and distinct gene expression patterns. Moreover, a variety of DNA copy number changes and gene expression-based classifiers have been described that could predict the outcome of neuroblastoma patients more precisely than established prognostic variables. In this review, the recent advances in the detection and evaluation of molecular prognostic markers for neuroblastoma patients are summarized, and their current and potential contribution to risk stratification systems is discussed.
Zusammenfassung
Das Neuroblastom weist eine bemerkenswerte klinische Vielfalt auf, die sowohl aggressive Erkrankungen mit tödlichem Ausgang als auch spontane Regressionen der Tumoren umfasst. Gegenwärtige Behandlungsprotokolle sehen daher für einige Patienten intensive multimodale Therapien vor, während bei anderen unter engmaschiger Kontrolle die Regression des Tumors abgewartet wird. Die exakte Vorhersage des zu erwartenden Verlaufs ist somit von essentieller Bedeutung für die Wahl einer adäquaten Therapie. Die Risikostratifizierung aktueller Behandlungsstudien beruht auf klinischen Variablen, wie Stadium und Alter bei Diagnose, sowie dem Vorhandensein molekularer Marker, wie einer Amplifikation des Onkogens MYCN oder einer Deletion des kurzen Arms von Chromosom 1. Es kommt jedoch immer noch zu fehlerhaften Risikoeinschätzungen, so dass die Verbesserung der Prognosebestimmung eine Herausforderung für die Neuroblastom-Forschung bleibt. In den vergangenen Jahren sind genomische Aberrationen und Genexpressionsprofile des Neuroblastoms detailliert charakterisiert worden. Diese Studien haben gezeigt, dass spezifische zytogenetische Veränderungen und Genexpressionsmuster den klinische Phänotyp präzise widerspiegeln und genutzt werden können, um den Krankheitsverlauf mit großer Genauigkeit vorherzusagen. In dieser Übersichtsarbeit werden die Fortschritte der Identifizierung und Evaluation molekularer Prognosemarker für das Neuroblastom zusammengefasst und ihr gegenwärtiger und potenzieller Beitrag zur Risikoabschätzung der Patienten diskutiert.
Key words
neuroblastoma - risk estimation - genomic aberration - gene expression - prognostic marker
Schlüsselwörter
Neuroblastom - Risikoabschätzung - genomische Aberration - Genexpression - Prognosemarker
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Correspondence
PD Dr. M. Fischer
Department of Pediatric Oncology and Hematology
University Children's Hospital of Cologne
Kerpener Str. 62
50924 Köln
Phone: +49/221/478 68 16
Fax: +49/221/478 46 89
Email: matthias.fischer@uk-koeln.de