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Epigenetische Aspekte bei Karzinomen der Kopf-Hals-Region

Epigenetic aspects in carcinomas of the head and neck

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Zusammenfassung

Plattenepithelkarzinome der Kopf-Hals-Region (HNSCC) zählen seit Jahren zu den weltweit häufigsten Krebsarten. Trotz vieler Bemühungen hat sich das 5-Jahres-Überleben bei Patienten mit HNSCC kaum verbessert. Um Fortschritte zu erzielen, ist es notwendig, die der Erkrankung zugrunde liegenden biologischen Prozesse besser zu verstehen. Neben den bekannten genetischen Veränderungen haben molekular-zytogenetische Untersuchungen bei HNSCC gezeigt, dass es weitere Veränderungen gibt, die mit Vermehrung und Verlust chromosomaler Bereiche einhergehen, für die jedoch die krankheitsverursachenden Gene bisher nicht identifiziert wurden. Darüber hinaus haben jüngste Forschungsergebnisse verdeutlicht, dass epigenetische Modifikationen wie die DNA-Methylierung eine wichtige Rolle spielen. So konnte gezeigt werden, dass bei HNSCC eine Reihe von Genen (z. B. das Tumorsuppressorgen CDKN2A sowie DAPK1, MGMT, TIMP3, TCF21, und C/EBPα) hypermethylierte Bereiche in regulatorischen DNA-Sequenzen aufweisen, wodurch ihre Expression verringert oder unterbunden wird. Die Hypermethylierung solcher Gene könnte als Biomarker zur Früherkennung von HNSCC genutzt werden und nicht zuletzt dadurch zur Verbesserung von Prävention und Therapieerfolg beitragen.

Abstract

For years, head and neck squamous cell carcinomas (HNSCC) have been among the leading cancers worldwide. Despite considerable efforts, the 5-year survival rate for HNSCC has not changed significantly. To improve this situation, it is necessary to understand the fundamental biological processes leading to the disease and its progression. In addition to known genetic changes in HNSCC, molecular cytogenetic investigations have identified chromosomal regions of gains and losses, but many of the responsible candidate genes have yet to be identified. Furthermore, recent results indicate the importance of epigenetic modifications in HNSCC, such as DNA methylation. Several genes, including the tumor suppressor CDKN2A and other candidates such as DAPK1, MGMT, TIMP3, TCF21, and C/EBPα, have been found to harbor hypermethylated regulatory sequences that lead to reduced expression or gene silencing. Hypermethylation in such genes could be used not only as biomarkers for the early detection of HNSCC but also to improve prevention strategies and therapy outcomes.

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Danksagung

Die Autoren danken Frau PD Dr. Odilia Popanda, Heidelberg, und Herrn Dr. Hardi Mundl, Basel, für die kritische Durchsicht des Manuskripts und die wertvollen Anregungen sowie Susanna Fuladdjusch für die technische Unterstützung. Epigenetische Projekte bei Kopf- und Hals-Tumoren in der Abteilung werden vom National Institute of Health (DE13123) unterstützt.

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  1. Abteilung Toxikologie und Krebsrisikofaktoren, Deutsches Krebsforschungszentrum (DKFZ), Im Neuenheimer Feld 280, 69120, Heidelberg, Deutschland

    P. Schmezer &  C. Plass

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Schmezer, P., Plass, C. Epigenetische Aspekte bei Karzinomen der Kopf-Hals-Region. HNO 56, 594–602 (2008). https://doi.org/10.1007/s00106-008-1720-3

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