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Genomic landscape of platinum resistant and sensitive testicular cancers.

Chey LovedayKevin LitchfieldPaula Z ProszekAlex J CornishFlavia SantoMax LevyGeoffrey MacintyreAmy HolryodPeter BroderickDarshna DudakiaBarbara BentonMaise Al BakirCrispin HileyEmily GristCharles SwantonRobert A HuddartTom PowlesSimon ChowdhuryJanet ShipleySimon O'ConnorJames D BrentonAlison ReidDavid Gonzalez de CastroRichard S HoulstonClare Turnbull
Published in: Nature communications (2020)
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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