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Copy number signatures and mutational processes in ovarian carcinoma.

ABSTRACT: The genomic complexity of profound copy number aberrations has prevented effective molecular stratification of ovarian cancers. Here, to decode this complexity, we derived copy number signatures from shallow whole-genome sequencing of 117 high-grade serous ovarian cancer (HGSOC) cases, which were validated on 527 independent cases. We show that HGSOC comprises a continuum of genomes shaped by multiple mutational processes that result in known patterns of genomic aberration. Copy number signature exposures at diagnosis predict both overall survival and the probability of platinum-resistant relapse. Measurement of signature exposures provides a rational framework to choose combination treatments that target multiple mutational processes.

SUBMITTER: Macintyre G 

PROVIDER: S-EPMC6130818 | biostudies-literature | 2018 Sep

REPOSITORIES: biostudies-literature

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Copy number signatures and mutational processes in ovarian carcinoma.

Macintyre Geoff G   Goranova Teodora E TE   De Silva Dilrini D   Ennis Darren D   Piskorz Anna M AM   Eldridge Matthew M   Sie Daoud D   Lewsley Liz-Anne LA   Hanif Aishah A   Wilson Cheryl C   Dowson Suzanne S   Glasspool Rosalind M RM   Lockley Michelle M   Brockbank Elly E   Montes Ana A   Walther Axel A   Sundar Sudha S   Edmondson Richard R   Hall Geoff D GD   Clamp Andrew A   Gourley Charlie C   Hall Marcia M   Fotopoulou Christina C   Gabra Hani H   Paul James J   Supernat Anna A   Millan David D   Hoyle Aoisha A   Bryson Gareth G   Nourse Craig C   Mincarelli Laura L   Sanchez Luis Navarro LN   Ylstra Bauke B   Jimenez-Linan Mercedes M   Moore Luiza L   Hofmann Oliver O   Markowetz Florian F   McNeish Iain A IA   Brenton James D JD  

Nature genetics 20180813 9

The genomic complexity of profound copy number aberrations has prevented effective molecular stratification of ovarian cancers. Here, to decode this complexity, we derived copy number signatures from shallow whole-genome sequencing of 117 high-grade serous ovarian cancer (HGSOC) cases, which were validated on 527 independent cases. We show that HGSOC comprises a continuum of genomes shaped by multiple mutational processes that result in known patterns of genomic aberration. Copy number signature  ...[more]

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