Zusammenfassung
Die Erforschung und Analyse der mit soliden Tumoren und hämatologischen Neoplasien einhergehenden genetischen Veränderungen spielen in der pädiatrischen Onkologie schon seit langem eine sehr wichtige Rolle. Die daraus resultierende Information ist nicht nur für diagnostische und differentialdiagnostische Belange sowie die Grundlagenforschung besonders wertvoll, sondern wird auch in zunehmendem Masse zur Therapiestratifizierung und Therapieüberwachung eingesetzt. In diesem Artikel gebe ich daher einen kurzen Überblick über ältere und neuere Methoden und beschreibe deren diagnostische Wertigkeit in den jeweiligen Zusammenhängen. Das Spektrum dieser Methoden reicht von der konventionellen Zytogenetik über eine Fluoreszenz-in-situ-Hybridisierung (FISH) und vielfältige RNA- und DNA-basierende qualitative und quantitative Polymerasekettenreaktionen (PCR) bis zu RNA- und DNA- basierenden Genom-Microarray-Methoden. Weiterhin präsentiere ich kurz die häufigsten und wichtigsten genetischen Subgruppen von hämatologischen Neoplasien und soliden Tumoren im Kindesalter, zusammen mit ihrer klinischen Bedeutung. Auf Grund ihres unterschiedlichen pathogenetischen Ursprungs unterscheiden sich sowohl die Art und Häufigkeit der im Kindesalter auftretenden Neoplasien als auch die damit assoziierten genetischen Merkmale grundlegend von jenen des späten Erwachsenenalters. Die ausführliche Analyse dieser genetischen Veränderung, speziell von Tumoren und Leukämien im Kindesalter, hilft uns daher nicht nur, die physiologischen und pathophysiologischen Vorgänge, welche zur Tumorentwicklung und -progression beitragen, besser zu verstehen. Wie bereits viele eindrucksvolle Beispiele der letzten Jahre belegen, dient sie letztendlich auch dazu, völlig neue therapeutische Konzepte zu entwickeln, die eine erfolgreiche individuelle und gleichzeitig nebenwirkungsfreiere Behandlung dieser Patienten ermöglichen.
Abstract
The investigation of genetic abnormalities that concur with hematological neoplasms and solid tumors play an important role in pediatric oncology. The retrieved information is not only extremely valuable for diagnostic, differential diagnostic and basic research purposes, but it is also increasingly used for treatment stratification and therapy surveillance. With that in mind, this article surveys the various older and newer diagnostic approaches and their special value in a particular context and provides examples for their practical applications. The vast spectrum of techniques ranges from conventional cytogenetics to a plethora of fluorescence in situ hybridization (FISH), various qualitative and quantitative DNA- and RNA-based polymerase chain reaction (PCR) as well as DNA- and RNA-based microarray methods. I will also briefly describe the most common and most important genetic subgroups of hematological neoplasms and solid tumors in childhood together with their biological and clinical significance. Owing to their diverse pathogenetic origin, the type, frequency as well as genetic make-up of the vast majority of tumors in children differ significantly from those encountered in late adulthood. The comprehensive analysis of these genetic alterations particularly in childhood tumors and leukemias not only improves our understanding of the physiological and pathophysiologcial processes leading to tumor manifestation and progression, but also adds significantly to the development of new improved therapeutic concepts which lead to a better, more individualized treatment with less adverse side effects, as many impressive examples have already illustrated within the last few years.
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