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Assigning evidence to actionability: An introduction to variant interpretation in precision cancer medicine.

Peter HorakJonas LeichsenringHannah GoldschmidSimon KreutzfeldtDaniel KazdalVeronica TeleanuVolker EndrisLaura GieldonMichael AllgäuerAnna-Lena VolckmarNicola DikowMarcus RennerMartina KirchnerRoland PenzelCarolin PloegerRegine BrandtHuriye Seker-CinJan BudcziesChristoph E HeiligOlaf NeumannChristian Patrick SchaafPeter SchirmacherStefan FröhlingAlbrecht Stenzinger
Published in: Genes, chromosomes & cancer (2021)
Modern concepts in precision cancer medicine are based on increasingly complex genomic analyses and require standardized criteria for the functional evaluation and reporting of detected genomic alterations in order to assess their clinical relevance. In this article, we propose and address the necessary steps in systematic variant evaluation consisting of bioinformatic analysis, functional annotation and clinical interpretation, focusing on the latter two aspects. We discuss the role and clinical application of current variant classification systems and point out their scope and limitations. Finally, we highlight the significance of the molecular tumor board as a platform for clinical decision-making based on genomic analyses.
Keyphrases
  • papillary thyroid
  • copy number
  • decision making
  • squamous cell
  • machine learning
  • deep learning
  • lymph node metastasis
  • childhood cancer
  • single molecule
  • single cell