Genomic landscape of platinum resistant and sensitive testicular cancers
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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 TurnbullAbstract
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.
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Publisher website (DOI) 10.1038/s41467-020-15768-x
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Europe PubMed Central 32366847
Pubmed 32366847
