Genomic landscape of platinum resistant and sensitive testicular cancers.

While most testicular germ cell tumours (TGCTs) exhibit exquisite sensitivity to platinum chemotherapy, ~10% are platinum resistant. To gain insight into the underlying mechanisms, we undertake whole exome sequencing and copy number analysis in 40 tumours from 26 cases with platinum-resistant TGCT, and combine this with published genomic data on an additional 624 TGCTs. We integrate analyses for driver mutations, mutational burden, global, arm-level and focal copy number (CN) events, and SNV and CN signatures. Albeit preliminary and observational in nature, these analyses provide support for a possible mechanistic link between early driver mutations in RAS and KIT and the widespread copy number events by which TGCT is characterised.

Nature communications. 2020 May 04*** epublish ***

Chey Loveday, Kevin Litchfield, Paula Z Proszek, Alex J Cornish, Flavia Santo, Max Levy, Geoff Macintyre, Amy Holryod, Peter Broderick, Darshna Dudakia, Barbara Benton, Maise Al Bakir, Crispin Hiley, Emily Grist, Charles Swanton, Robert Huddart, Tom Powles, Simon Chowdhury, Janet Shipley, Simon O'Connor, James D Brenton, Alison Reid, David Gonzalez de Castro, Richard S Houlston, Clare Turnbull

Division of Genetics & Epidemiology, The Institute of Cancer Research, London, UK., The Centre for Molecular Pathology, The Royal Marsden NHS Trust, Sutton, London, UK., Cancer Research UK Cambridge Institute, University of Cambridge, Cambridge, UK., Cancer Research UK Lung Cancer Centre of Excellence, University College London Cancer Institute, London, UK., Division of Molecular Pathology, The Institute of Cancer Research, London, UK., Academic Radiotherapy Unit, Institute of Cancer Research, London, UK., Barts Cancer Institute, Queen Mary University, London, UK., Department of Oncology, Guys and St Thomas' NHS Foundation Trust, London, UK., Academic Uro-oncology Unit, The Royal Marsden NHS Foundation Trust, Sutton, London, UK., Centre for Cancer Research and Cell Biology, Queen's University Belfast, Belfast, UK., Division of Genetics & Epidemiology, The Institute of Cancer Research, London, UK. .

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