Genomic landscape of platinum resistant and sensitive testicular cancers.

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.

Authors:: C Loveday, K Litchfield, PZ Proszek, AJ Cornish, F Santo, M Levy, G Macintyre, A Holryod, P Broderick, D Dudakia, B Benton, MA Bakir, C Hiley, E Grist, C Swanton, R Huddart, T Powles, S Chowdhury, J Shipley, S O'Connor, JD Brenton, A Reid, DG de Castro, RS Houlston, C Turnbull

Themes