Copy number signatures and mutational processes in ovarian carcinoma.

G Macintyre; TE Goranova; Silva D De; D Ennis; AM Piskorz; M Eldridge; D Sie; LA Lewsley; A Hanif; C Wilson; S Dowson; RM Glasspool; M Lockley; JD Brenton

doi:10.1038/s41588-018-0179-8

Copy number signatures and mutational processes in ovarian carcinoma.

G Macintyre, TE Goranova, Silva D De, D Ennis, AM Piskorz, M Eldridge, D Sie, LA Lewsley, A Hanif, C Wilson, S Dowson, RM Glasspool, M Lockley, JD Brenton

Research output: Contribution to journal › Article › peer-review

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.

Original language	English
Pages (from-to)	1262-1270
Journal	Nature Genetics
Volume	50
DOIs	https://doi.org/10.1038/s41588-018-0179-8
Publication status	Published - Aug 2018

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title = "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.",

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doi = "10.1038/s41588-018-0179-8",

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AU - Macintyre, G

AU - Goranova, TE

AU - De, Silva D

AU - Ennis, D

AU - Piskorz, AM

AU - Eldridge, M

AU - Sie, D

AU - Lewsley, LA

AU - Hanif, A

AU - Wilson, C

AU - Dowson, S

AU - Glasspool, RM

AU - Lockley, M

AU - Brenton, JD

PY - 2018/8

Y1 - 2018/8

N2 - 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.

AB - 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.

UR - http://europepmc.org/abstract/med/30104763

U2 - 10.1038/s41588-018-0179-8

DO - 10.1038/s41588-018-0179-8

M3 - Article

C2 - 30104763

SN - 1061-4036

VL - 50

SP - 1262

EP - 1270

JO - Nature Genetics

JF - Nature Genetics

ER -

Copy number signatures and mutational processes in ovarian carcinoma.

Abstract

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