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'ConnorJames D Brenton, Alison Reid, David Gonzalez de Castro, Richard S Houlston, Clare Turnbull

Research output: Contribution to journalArticlepeer-review

6 Citations (Scopus)
26 Downloads (Pure)

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.

Original languageEnglish
Pages (from-to)2189
JournalNature Communications
Volume11
Issue number1
DOIs
Publication statusPublished - 04 May 2020

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