Copy number signatures and mutational processes in ovarian carcinoma

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

doi:https://doi.org/10.1038/s41588-018-0179-8

Copy number signatures and mutational processes in ovarian carcinoma

Geoff Macintyre, Teodora E. Goranova, Dilrini De Silva, Darren Ennis, Anna M. Piskorz, Matthew Eldridge, Daoud Sie, Liz Anne Lewsley, Aishah Hanif, Cheryl Wilson, Suzanne Dowson, Rosalind M. Glasspool, Michelle Lockley, Elly Brockbank, Ana Montes, Axel Walther, Sudha Sundar, Richard Edmondson, Geoff D. Hall, Andrew ClampCharlie Gourley, Marcia Hall, Christina Fotopoulou, Hani Gabra, James Paul, Anna Supernat, David Millan, Aoisha Hoyle, Gareth Bryson, Craig Nourse, Laura Mincarelli, Luis Navarro Sanchez, Bauke Ylstra, Mercedes Jimenez-Linan, Luiza Moore, Oliver Hofmann, Florian Markowetz, Iain A. McNeish, James D. Brenton

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

250 Citations (Scopus)

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
Number of pages	9
Journal	Nature Genetics
Volume	50
Issue number	9
DOIs	https://doi.org/10.1038/s41588-018-0179-8
Publication status	Published - 1 Sept 2018

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Macintyre, G., Goranova, T. E., De Silva, D., Ennis, D., Piskorz, A. M., Eldridge, M., Sie, D., Lewsley, L. A., Hanif, A., Wilson, C., Dowson, S., Glasspool, R. M., Lockley, M., Brockbank, E., Montes, A., Walther, A., Sundar, S., Edmondson, R., Hall, G. D., ... Brenton, J. D. (2018). Copy number signatures and mutational processes in ovarian carcinoma. Nature Genetics, 50(9), 1262-1270. https://doi.org/10.1038/s41588-018-0179-8

@article{11c76a71379b4cdb9b06c108e8a5a8cd,

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.",

author = "Geoff Macintyre and Goranova, {Teodora E.} and {De Silva}, Dilrini and Darren Ennis and Piskorz, {Anna M.} and Matthew Eldridge and Daoud Sie and Lewsley, {Liz Anne} and Aishah Hanif and Cheryl Wilson and Suzanne Dowson and Glasspool, {Rosalind M.} and Michelle Lockley and Elly Brockbank and Ana Montes and Axel Walther and Sudha Sundar and Richard Edmondson and Hall, {Geoff D.} and Andrew Clamp and Charlie Gourley and Marcia Hall and Christina Fotopoulou and Hani Gabra and James Paul and Anna Supernat and David Millan and Aoisha Hoyle and Gareth Bryson and Craig Nourse and Laura Mincarelli and Sanchez, {Luis Navarro} and Bauke Ylstra and Mercedes Jimenez-Linan and Luiza Moore and Oliver Hofmann and Florian Markowetz and McNeish, {Iain A.} and Brenton, {James D.}",

year = "2018",

month = sep,

day = "1",

doi = "https://doi.org/10.1038/s41588-018-0179-8",

language = "English",

volume = "50",

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journal = "Nature Genetics",

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Macintyre, G, Goranova, TE, De Silva, D, Ennis, D, Piskorz, AM, Eldridge, M, Sie, D, Lewsley, LA, Hanif, A, Wilson, C, Dowson, S, Glasspool, RM, Lockley, M, Brockbank, E, Montes, A, Walther, A, Sundar, S, Edmondson, R, Hall, GD, Clamp, A, Gourley, C, Hall, M, Fotopoulou, C, Gabra, H, Paul, J, Supernat, A, Millan, D, Hoyle, A, Bryson, G, Nourse, C, Mincarelli, L, Sanchez, LN, Ylstra, B, Jimenez-Linan, M, Moore, L, Hofmann, O, Markowetz, F, McNeish, IA & Brenton, JD 2018, 'Copy number signatures and mutational processes in ovarian carcinoma', Nature Genetics, vol. 50, no. 9, pp. 1262-1270. https://doi.org/10.1038/s41588-018-0179-8

TY - JOUR

T1 - Copy number signatures and mutational processes in ovarian carcinoma

AU - Macintyre, Geoff

AU - Goranova, Teodora E.

AU - De Silva, Dilrini

AU - Ennis, Darren

AU - Piskorz, Anna M.

AU - Eldridge, Matthew

AU - Sie, Daoud

AU - Lewsley, Liz Anne

AU - Hanif, Aishah

AU - Wilson, Cheryl

AU - Dowson, Suzanne

AU - Glasspool, Rosalind M.

AU - Lockley, Michelle

AU - Brockbank, Elly

AU - Montes, Ana

AU - Walther, Axel

AU - Sundar, Sudha

AU - Edmondson, Richard

AU - Hall, Geoff D.

AU - Clamp, Andrew

AU - Gourley, Charlie

AU - Hall, Marcia

AU - Fotopoulou, Christina

AU - Gabra, Hani

AU - Paul, James

AU - Supernat, Anna

AU - Millan, David

AU - Hoyle, Aoisha

AU - Bryson, Gareth

AU - Nourse, Craig

AU - Mincarelli, Laura

AU - Sanchez, Luis Navarro

AU - Ylstra, Bauke

AU - Jimenez-Linan, Mercedes

AU - Moore, Luiza

AU - Hofmann, Oliver

AU - Markowetz, Florian

AU - McNeish, Iain A.

AU - Brenton, James D.

PY - 2018/9/1

Y1 - 2018/9/1

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.

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U2 - https://doi.org/10.1038/s41588-018-0179-8

DO - https://doi.org/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

IS - 9

ER -

Copy number signatures and mutational processes in ovarian carcinoma

Abstract

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