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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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DNA Copy Number Variations
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Drug Resistance, Neoplasm / drug effects*
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Exome Sequencing / methods
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Genetic Predisposition to Disease / genetics
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Genomics / methods*
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Humans
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Male
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Mutation
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Neoplasms, Germ Cell and Embryonal / drug therapy*
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Neoplasms, Germ Cell and Embryonal / genetics
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Neoplasms, Germ Cell and Embryonal / metabolism
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Organoplatinum Compounds / therapeutic use
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Platinum / therapeutic use*
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Proto-Oncogene Proteins c-kit / genetics
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Proto-Oncogene Proteins c-kit / metabolism
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Signal Transduction / genetics
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Testicular Neoplasms / drug therapy*
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Testicular Neoplasms / genetics
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Testicular Neoplasms / metabolism
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ras Proteins / genetics
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ras Proteins / metabolism
Substances
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Organoplatinum Compounds
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Platinum
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Proto-Oncogene Proteins c-kit
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ras Proteins
Supplementary concepts
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Testicular Germ Cell Tumor