Copy-number signatures and mutational processes in ovarian carcinoma
Teodora E. Goranova,
Dilrini De Silva,
Anna M. Piskorz,
Matthew D Eldridge,
Rosalind M. Glasspool,
Geoff D. Hall,
Luis Navarro Sanchez,
Posted 09 Aug 2017
bioRxiv DOI: 10.1101/174201 (published DOI: 10.1038/s41588-018-0179-8)
Posted 09 Aug 2017
Genomic complexity from profound copy-number aberration has prevented effective molecular stratification of ovarian and other cancers. Here we present a method for copy-number signature identification that decodes this complexity. We derived eight signatures using 117 shallow whole-genome sequenced high-grade serous ovarian cancer cases, which were validated on a further 497 cases. Mutational processes underlying the copy-number signatures were identified, including breakage-fusion-bridge cycles, homologous recombination deficiency and whole-genome duplication. We show that most tumours are heterogeneous and harbour multiple signature exposures. We also demonstrate that copy number signatures predict overall survival and changes in signature exposure observed in response to chemotherapy suggest potential treatment strategies.
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