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Variant classification in precision oncology

Next-generation sequencing has become a cornerstone of therapy guidance in cancer precision medicine and an indispensable research tool in translational oncology. Its rapidly increasing use during the last decade has expanded the options for targeted tumor therapies, and molecular tumor boards have...

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Main Authors: Leichsenring, Jonas (Author) , Horak, Peter (Author) , Heining, Christoph (Author) , Christopoulos, Petros (Author) , Volckmar, Anna-Lena (Author) , Neumann, Olaf (Author) , Kirchner, Martina (Author) , Budczies, Jan (Author) , Heilig, Christoph E. (Author) , Kazdal, Daniel (Author) , Allgäuer, Michael (Author) , Harms, Alexander (Author) , Rempel, Eugen (Author) , Thomas, Michael (Author) , Longerich, Thomas (Author) , Schirmacher, Peter (Author) , Penzel, Roland (Author) , Endris, Volker (Author) , Fröhling, Stefan (Author) , Stenzinger, Albrecht (Author)
Format: Article (Journal)
Language:English
Published: 22 April 2019
In: International journal of cancer
Year: 2019, Volume: 145, Issue: 11, Pages: 2996-3010
ISSN:1097-0215
DOI:10.1002/ijc.32358
Online Access:Verlag, Volltext: https://doi.org/10.1002/ijc.32358
Verlag: https://onlinelibrary.wiley.com/doi/abs/10.1002/ijc.32358
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Author Notes:Jonas Leichsenring, Peter Horak, Simon Kreutzfeldt, Christoph Heining, Petros Christopoulos, Anna-Lena Volckmar, Olaf Neumann, Martina Kirchner, Carolin Ploeger, Jan Budczies, Christoph E. Heilig, Barbara Hutter, Martina Fröhlich, Sebastian Uhrig, Daniel Kazdal, Michael Allgäuer, Alexander Harms, Eugen Rempel, Ulrich Lehmann, Michael Thomas, Nicole Pfarr, Ninel Azoitei, Irina Bonzheim, Ralf Marienfeld, Peter Möller, Martin Werner, Falko Fend, Melanie Boerries, Nikolas von Bubnoff, Silke Lassmann, Thomas Longerich, Michael Bitzer, Thomas Seufferlein, Nisar Malek, Wilko Weichert, Peter Schirmacher, Roland Penzel, Volker Endris, Benedikt Brors, Frederick Klauschen, Hanno Glimm, Stefan Fröhling, Albrecht Stenzinger
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Summary:Next-generation sequencing has become a cornerstone of therapy guidance in cancer precision medicine and an indispensable research tool in translational oncology. Its rapidly increasing use during the last decade has expanded the options for targeted tumor therapies, and molecular tumor boards have grown accordingly. However, with increasing detection of genetic alterations, their interpretation has become more complex and error-prone, potentially introducing biases and reducing benefits in clinical practice. To facilitate interdisciplinary discussions of genetic alterations for treatment stratification between pathologists, oncologists, bioinformaticians, genetic counselors and medical scientists in specialized molecular tumor boards, several systems for the classification of variants detected by large-scale sequencing have been proposed. We review three recent and commonly applied classifications and discuss their individual strengths and weaknesses. Comparison of the classifications underlines the need for a clinically useful and universally applicable variant reporting system, which will be instrumental for efficient decision making based on sequencing analysis in oncology. Integrating these data, we propose a generalizable classification concept featuring a conservative and a more progressive scheme, which can be readily applied in a clinical setting.
Item Description:Gesehen am 29.10.2019
Physical Description:Online Resource
ISSN:1097-0215
DOI:10.1002/ijc.32358

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