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Genomic landscape of platinum resistant and sensitive testicular cancers

Published version
Peer-reviewed

Type

Article

Change log

Authors

Loveday, Chey 
Brenton, James D 

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 undertook undertake whole exome sequencing and copy number analysis in 40 tumours from 26 cases with platinum-resistant TGCT, and combined this with published genomic data on an additional 624 TGCTs. We integrated 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 the first 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.

Description

Keywords

DNA Copy Number Variations, Drug Resistance, Neoplasm, Genetic Predisposition to Disease, Genomics, Humans, Male, Mutation, Neoplasms, Germ Cell and Embryonal, Organoplatinum Compounds, Platinum, Proto-Oncogene Proteins c-kit, Signal Transduction, Testicular Neoplasms, Exome Sequencing, ras Proteins

Journal Title

Nature Communications

Conference Name

Journal ISSN

2041-1723
2041-1723

Volume Title

11

Publisher

Springer Nature
Sponsorship
Cancer Research UK (CB4150)
Cancer Research UK (C14303/A17197)
Cancer Research UK (22905)
Cancer Research UK (15601)