The Genetics of Uveal Melanoma: Overview and Clinical Relevance

Aline Isabel Riechardt; Emine Kilic; Antonia M. Joussen

doi:10.1055/a-1513-0789

Klinische Monatsblätter für Augenheilkunde, Table of Contents

Klin Monbl Augenheilkd 2021; 238(07): 773-780
DOI: 10.1055/a-1513-0789

Übersicht

Genetik der Aderhautmelanome: Übersicht und klinische Relevanz

Article in several languages: English | deutsch

Authors

Aline Isabel Riechardt

¹Klinik für Augenheilkunde, Charité – Universitätsmedizin Berlin, Deutschland
Emine Kilic

²Department of Ophthalmology, Erasmus Medical Center, Rotterdam, Niederlande
Antonia M. Joussen

¹Klinik für Augenheilkunde, Charité – Universitätsmedizin Berlin, Deutschland

Abstract

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

Full Text

References

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