Criteria of the German Consortium for Hereditary Breast and Ovarian Cancer for the Classification of Germline Sequence Variants in Risk Genes for Hereditary Breast and Ovarian Cancer

Barbara Wappenschmidt; Jan Hauke; Ulrike Faust; Dieter Niederacher; Lisa Wiesmüller; Gunnar Schmidt; Evi Groß; Andrea Gehrig; Christian Sutter; Juliane Ramser; Andreas Rump; Norbert Arnold; Alfons Meindl

doi:10.1055/a-1110-0909

Geburtshilfe und Frauenheilkunde, Table of Contents

CC BY-NC-ND 4.0 · Geburtshilfe Frauenheilkd 2020; 80(04): 410-429
DOI: 10.1055/a-1110-0909

GebFra Science

Review/Übersicht

Georg Thieme Verlag KG Stuttgart · New York

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

Article in several languages: English | deutsch

Authors

Barbara Wappenschmidt

¹Zentrum familiärer Brust- und Eierstockkrebs, Universitätsklinikum Köln, Köln, Germany
Jan Hauke

¹Zentrum familiärer Brust- und Eierstockkrebs, Universitätsklinikum Köln, Köln, Germany
Ulrike Faust

²Institut für Medizinische Genetik und Angewandte Genomik, Universität Tübingen, Tübingen, Germany
Dieter Niederacher

³Klinik für Frauenheilkunde und Geburtshilfe, Universitätsklinikum Düsseldorf, Düsseldorf, Germany
Lisa Wiesmüller

⁴Frauenklinik, Sektion Gynäkologische Onkologie, Uniklinik Ulm, Ulm, Germany
Gunnar Schmidt

⁵Institut für Humangenetik, Medizinische Hochschule Hannover, Hannover, Germany
Evi Groß

⁶Klinik und Poliklinik für Frauenheilkunde und Geburtshilfe, Klinikum der Universität München, Campus Großhadern, München, Germany
Andrea Gehrig

⁷Institut für Humangenetik, Universität Würzburg, Würzburg, Germany
Christian Sutter

⁸Institut für Humangenetik, Universität Heidelberg, Heidelberg, Germany
Juliane Ramser

⁹Frauenklinik der Technischen Universität München, Klinikum rechts der Isar, München, Germany
Andreas Rump

¹⁰Institut für klinische Genetik, Technische Universität Dresden, Dresden, Germany
Norbert Arnold

¹¹Universitätsklinikum Kiel, Klinik für Gynäkologie und Geburtshilfe, Kiel, Germany

¹²Institut für Klinische Molekularbiologie, Universitätsklinikum Kiel, Kiel, Germany
Alfons Meindl

⁶Klinik und Poliklinik für Frauenheilkunde und Geburtshilfe, Klinikum der Universität München, Campus Großhadern, München, Germany

⁹Frauenklinik der Technischen Universität München, Klinikum rechts der Isar, München, Germany

Abstract

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

Full Text

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