Genomic landscape of platinum resistant and sensitive testicular cancers

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 Castro, Richard S. Houlston and Clare Turnbull ()
Additional contact information
Chey Loveday: The Institute of Cancer Research
Kevin Litchfield: The Institute of Cancer Research
Paula Z. Proszek: The Royal Marsden NHS Trust
Alex J. Cornish: The Institute of Cancer Research
Flavia Santo: The Royal Marsden NHS Trust
Max Levy: The Institute of Cancer Research
Geoff Macintyre: University of Cambridge
Amy Holryod: The Institute of Cancer Research
Peter Broderick: The Institute of Cancer Research
Darshna Dudakia: The Institute of Cancer Research
Barbara Benton: The Institute of Cancer Research
Maise Al Bakir: University College London Cancer Institute
Crispin Hiley: University College London Cancer Institute
Emily Grist: The Institute of Cancer Research
Charles Swanton: University College London Cancer Institute
Robert Huddart: Institute of Cancer Research
Tom Powles: Queen Mary University
Simon Chowdhury: Guys and St Thomas’ NHS Foundation Trust
Janet Shipley: The Institute of Cancer Research
Simon O’Connor: The Royal Marsden NHS Trust
James D. Brenton: University of Cambridge
Alison Reid: The Royal Marsden NHS Foundation Trust
David Gonzalez Castro: Queen’s University Belfast
Richard S. Houlston: The Institute of Cancer Research
Clare Turnbull: The Institute of Cancer Research

Nature Communications, 2020, vol. 11, issue 1, 1-12

Abstract: Abstract 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.

Date: 2020
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DOI: 10.1038/s41467-020-15768-x

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