Genomic landscape of platinum resistant and sensitive testicular cancers.
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Publication Date
2020-05-04Author
Loveday, C
Litchfield, K
Proszek, PZ
Cornish, AJ
Santo, F
Levy, M
Macintyre, G
Holryod, A
Broderick, P
Dudakia, D
Benton, B
Bakir, MA
Hiley, C
Grist, E
Swanton, C
Huddart, R
Powles, T
Chowdhury, S
Shipley, J
O'Connor, S
Brenton, JD
Reid, A
de Castro, DG
Houlston, RS
Turnbull, C
Type
Journal Article
Metadata
Show full item recordAbstract
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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Licenseref URL
http://creativecommons.org/licenses/by/4.0/Version of record
Subject
Humans
Neoplasms, Germ Cell and Embryonal
Testicular Neoplasms
Genetic Predisposition to Disease
Platinum
Organoplatinum Compounds
ras Proteins
Genomics
Signal Transduction
Drug Resistance, Neoplasm
Mutation
Male
Proto-Oncogene Proteins c-kit
DNA Copy Number Variations
Whole Exome Sequencing
Research team
Cancer Genomics
Sarcoma Molecular Pathology
Clinical Academic Radiotherapy (Huddart)
Language
eng
Date accepted
2020-03-23
License start date
2020-05-04
Citation
Nature communications, 2020, 11 (1), pp. 2189 - ?