Genetik der Aderhautmelanome: Übersicht und klinische Relevanz

Zusammenfassung

Die letzte Dekade zeichnet sich durch einen erheblichen Erkenntniszuwachs bez. der Genetik der uvealen Melanome aus. Es zeigte sich, dass das uveale Melanom grundlegende Unterschiede zu den nicht uvealen Melanomen aufweist und somit einen eigenständigen genetischen Subtyp darstellt. Im Vergleich zu anderen Tumoren weist das uveale Melanom eine geringe Mutationslast auf. Es finden sich wiederkehrende chromosomale Aberrationen mit Verlusten von 1p, 6q, 8p und 16q, Gewinnen von 6p und 8q sowie dem Vorliegen einer Monosomie 3. Als signifikant mutierte Gene konnten GNAQ, GNA11, PLCB4, CYSLTR2, MAPKAPK5 sowie BAP1, SF3B1, SRSF2 und EIF1AX identifiziert werden, wobei Letztere mit einem erhöhten Metastasierungsrisiko assoziiert sind. Selten kann zudem eine BAP1-Keimbahnmutation vorliegen. Diese Variante ist außer mit dem uvealen Melanom auch mit weiteren Tumoren vergesellschaftet. In diesem Fall sollte eine erweiterte Abklärung und eine humangenetische Beratung erfolgen sowie eine zusätzliche Untersuchung der Familienangehörigen angeboten werden. Die Erkenntnisse bez. der genetischen Eigenarten lassen sich diagnostisch und prognostisch bereits routinemäßig einsetzen. Eine zielgerichtete genotypbasierte Therapie des uvealen Melanoms steht derzeit noch aus.

Schlüsselwörter

Aderhautmelanom - uveales Melanom - chromosomale Aberration - genetische Evolution - BAP1-Tumorprädispositionssyndrom - Genetik

Publication History

Received: 29 January 2021

Accepted: 18 May 2021

Article published online:
10 August 2021

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