Aktuelles zur klinischen Bedeutung genetischer Veränderungen bei malignen Melanomen der Uvea

Zusammenfassung

Das Aderhautmelanom ist der häufigste primäre intraokulare Tumor in der kaukasischen Bevölkerung. In Deutschland kommt es zu circa 500 Neuerkrankungen pro Jahr. Die höchste Inzidenzrate liegt um das 70. Lebensjahr. Bei etwa der Hälfte der Patienten entwickeln sich Metastasen, die auch noch viele Jahre nach erfolgreicher Therapie des Primärtumors erstmals auftreten können und bei den meisten Patienten die Leber betreffen. Das Aderhautmelanom lässt sich allein auf Grundlage des Chromosom-3-Status im Primärtumor in 2 Risikogruppen einteilen, die sich wesentlich in ihrer Metastasierungsneigung unterscheiden. Die Tumoren mit einem sehr hohen Metastasierungsrisiko haben eine Monosomie 3 (M3). Tumoren mit Disomie 3 (D3) hingegen zeigen ein sehr geringes Metastasierungsrisiko. Ein prognostisches Testen des Primärtumors ist auf Wunsch des Patienten möglich. Tumorproben können sowohl mit Hilfe einer transretinalen oder transkleralen Biopsie, als auch nach Enukleation gewonnen werden. Aktuell ergibt sich hieraus jedoch noch keine therapeutische Konsequenz. Vor kurzem sind mit GNAQ, GNA11, BAP1, SF3B1 und EIF1AX wesentliche Schlüsselgene der Aderhautmelanomentstehung identifiziert worden. Die Erstellung eines Mutationsprofils, ergänzend zur Chromosom-3-Untersuchung, wird die Klassifizierung bzw. Subklassifizierung eines Aderhautmelanoms verfeinern und möglicherweise therapeutische sowie auch diagnostische Konzepte beeinflussen. Erbliche Mutationen im Tumorsuppressorgen BAP1 sind mit einem erhöhten Risiko für unterschiedliche Tumorerkrankungen assoziiert. Der Nachweis einer solchen Keimbahnmutation bei einem Patienten sollte Vorsorgeuntersuchungen für die damit verbundenen Tumorentitäten zur Folge haben. Zusätzlich sollte Familienangehörigen eine Untersuchung auf diese BAP1-Mutation angeboten werden.

Abstract

Uveal melanoma is the most common primary intraocular tumour in Caucasians. There are approximately 500 new cases of uveal melanoma in Germany per year and the incidence rate peaks at the age of 70 years. Half of all uveal melanoma patients develop metastatic disease, which can be observed even many years after successful treatment of the primary tumour. In most cases the liver is the location of first manifestation. Based on the chromosome 3 status uveal melanomas can be divided into two major classes that differ in their metastatic potential. Tumours with a high risk to metastasise usually show monosomy 3, whereas tumours showing disomy 3 rarely metastasise. If a patient wishes to know about his individual risk, prognostic testing of the primary tumour tissue can be performed after obtaining tumour material via transscleral or transretinal biopsy, or by enucleation. To date results of prognostic testing do not influence therapeutic strategies. Recently, major key genes involved in uveal melanoma development, GNAQ, GNA11, BAP1, SF3B1 and EIF1AX, have been identified. Mutation profiling, in addition to chromosomal 3 analysis, will further refine the classification or subclassification of uveal melanomas and will hopefully influence diagnostic or therapeutic concepts. Hereditary mutations in tumour suppressor gene BAP1 are associated with an increased risk for different tumour entities. Detection of germ line mutations in this tumour suppressor gene should implicate further general screening examinations of the patient to be able to detect these tumour entities. Moreover relatives of these patients should be offered a screening for BAP1 mutation.

Schlüsselwörter

Genetik - okuläre Tumoren - Chorioidea

Key words

genetics - ocular tumours - choroid

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