Kriterien des Deutschen Konsortiums Familiärer Brust- und Eierstockkrebs zur Klassifizierung von Keimbahn-Sequenzvarianten in Risikogenen für familiären Brust- und Eierstockkrebs

Zusammenfassung

Das Deutsche Konsortium für Familiären Brust- und Eierstockkrebs (GC-HBOC) etablierte vor über 10 Jahren eine Expertengruppe (VUS Task Force), um die von den einzelnen Zentren des GC-HBOC an die zentrale Datenbank in Leipzig gemeldeten Varianten hinsichtlich ihrer Klassifizierung zu überprüfen und ggf. nach aktueller Datenlage neu einzustufen. Die innerhalb der VUS-Task Force konsentierten Variantenbewertungen und resultierenden -klassifizierungen werden in einer zentralen Datenbank hinterlegt und sind als Grundlage zu berücksichtigen, um eine einheitliche Bewertung bereits bekannter wie auch neu identifizierter Varianten innerhalb der verschiedenen Zentren des GC-HBOC zu gewährleisten. Die standardisierte VUS-Bewertung durch die VUS Task Force ist ein zentrales Element des vom GC-HBOC ebenfalls etablierten Recall-Systems. Dieses dient der Weitergabe der Informationen an die in den Zentren betreuten Familien im Falle einer aufgrund neuer Erkenntnisse aktualisierten Neubewertung von bereits klassifizierten Varianten. Die in Anlehnung an international etablierte Bewertungsverfahren (IARC, ACMG, ENIGMA) angepassten Bewertungsalgorithmen der VUS Task Force werden in diesem Artikel anhand der zugrundeliegenden Entscheidungskriterien präsentiert, die gemäß eines priorisierenden Fließschemas zum Klassifizierungsergebnis führen. Weiterhin werden genspezifische Regelungen und Besonderheiten, die für einzelne mit Brust- und/oder Eierstockkrebs assoziierte Risikogene zu berücksichtigen sind, in einzelnen Unterkapiteln dargelegt. Um dem Umfang und der Dynamik des aktuellen Wissens zur Variantenbewertung gerecht zu werden, sind neben umfangreichen Literaturverweisen insbesondere auch die URLs von relevanten Datenbanken angegeben. In Zukunft sollen an neue Erkenntnisse angepasste Kriterien auf der Webseite von GC-HBOC (https://www.konsortium-familiaerer-brustkrebs.de/) veröffentlicht werden.

Schlüsselwörter

familiärer Brust-/Eierstockkrebs - Klassifikation genetischer Varianten - Risikogene

• References/Literatur

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