Zusammenfassung
Systembiologische Ansätze für Mutationen (Exomanalysen und „targeted sequencing“) und Genexpressionsanalysen (transkriptomweites „Genexpressions-Profiling“) stellen in der Kopf-Hals-Onkologie ein neues wachsendes Gebiet dar, das neben medizinisch biologischer Kompetenz auch zunehmend bioinformatisches Spezialwissen erfordert. Für die Plattenepithelkarzinome des Kopf-Hals-Bereichs („head and neck squamous cell carcinoma“, HNSCC) stellen die bisherigen molekulargenetischen Einzel-Gen- und Signalwegbetrachtungen Grundlagenforschung dar. Diese hat mittlerweile an verschiedenen Stellen wesentliche Erweiterungen durch systembiologische Ansätze, welche zu relevanten translationalen klinischen Forschungsfeldern herangewachsen sind. Heutzutage ist bekannt, dass Humanpapillomvirus(HPV)16 an verschiedenen Stellen mit genetischen Veränderungen assoziiert ist, aber auch auf der Methylierungsebene funktionellen Einfluss auf nicht in ihrer Basensequenz alterierte Gene ausübt. Verschiedene Konsortien fanden in Transkriptomanalysen übereinstimmende Cluster der Genexpression und HPV16-Assoziationen mit dem Spektrum somatischer Mutationen. Die bei HPV16-getriebenen HNSCC ermittelte differenzielle Methylierung von Genpromotoren erwies sich als prädiktiv für das Überleben auch bei HNSCC-Patienten ohne HPV-Nachweis. Die Autoren stellen eine Übersicht einiger translational relevanter Erkenntnisse dar und wagen einen Ausblick auf mögliche zukünftige klinische Entwicklungen.
Abstract
Systems biology approaches for mutational (exome analysis and targeted sequencing) and gene expression analysis (transcriptome-wide gene expression profiling) represent a new and growing scientific field in head and neck oncology. In addition to medical biological expertise, bioinformatic assistance is increasingly required. For squamous cell head and neck cancer (HNSCC), the recent molecular genetic single-gene and signal pathway observations represent basic research. Important aspects of this have now been significantly enhanced by systems biology approaches, which have grown into relevant areas of translational clinical research. It is now known that HPV16 is associated with genetic alterations at various locations, but also that it functionally affects genes not altered in their base sequence at the level of methylation. In transcriptome analyses, various consortia found matching clusters of gene expression and HPV16 association with the spectrum of somatic mutations. The differential methylation of gene promoters discovered in HPV16-driven HNSCC proved predictive for survival—even in HNSCC patients without HPV detection. The authors present an overview of some translationally relevant findings and venture an outlook on possible future clinical developments.
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A. Dietz, M. Loeffler, M. Rosolowski, M. Kreuz, F. Lordick, M. Knödler, C. Mozet und G. Wichmann geben an, dass kein Interessenkonflikt besteht.
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Dietz, A., Loeffler, M., Rosolowski, M. et al. Genexpressionsanalysen und ihr möglicher klinischer Nutzen in der Betrachtung der Kopf-Hals-Karzinome. HNO 63, 773–785 (2015). https://doi.org/10.1007/s00106-015-0078-6
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DOI: https://doi.org/10.1007/s00106-015-0078-6