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Copy-number signatures and mutational processes in ovarian carcinoma

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Title: Copy-number signatures and mutational processes in ovarian carcinoma
Authors: Macintyre, G
Goranova, TE
De Silva, D
Ennis, D
Piskorz, AM
Eldridge, M
Sie, D
Lewsley, L-A
Hanif, A
Wilson, C
Dowson, S
Glasspool, RM
Lockley, M
Brockbank, E
Montes, A
Walther, A
Sundar, SS
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
Navarro Sanchez, L
Ylstra, B
Jimenez-Linan, M
Moore, L
Hofmann, O
Markowetz, F
McNeish, IA
Brenton, JD
Item Type: Journal Article
Abstract: The genomic complexity of profound copy-number aberration has prevented effective molecular stratification of ovarian cancers. 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. Measuring signature exposures provides a rational framework to choose combination treatments that target multiple mutational processes.
Issue Date: 13-Aug-2018
Date of Acceptance: 19-Jun-2018
URI: http://hdl.handle.net/10044/1/61593
DOI: https://dx.doi.org/10.1038/s41588-018-0179-8
ISSN: 1061-4036
Publisher: Nature Publishing Group
Start Page: 1262
End Page: 1270
Journal / Book Title: Nature Genetics
Volume: 50
Copyright Statement: © 2019 Springer Nature Publishing AG
Sponsor/Funder: Imperial College Healthcare NHS Trust- BRC Funding
Cancer Research UK
Funder's Grant Number: RDB01
RG71079
Keywords: Science & Technology
Life Sciences & Biomedicine
Genetics & Heredity
TANDEM DUPLICATOR PHENOTYPE
GRADE SEROUS CARCINOMA
BREAST-CANCER
OPEN-LABEL
R PACKAGE
DNA
REVEALS
QUANTIFICATION
IDENTIFICATION
AMPLIFICATION
Adult
Aged
Aged, 80 and over
DNA Copy Number Variations
Female
Genomics
Humans
Middle Aged
Mutation
Neoplasm Recurrence, Local
Ovarian Neoplasms
Whole Genome Sequencing
Humans
Ovarian Neoplasms
Neoplasm Recurrence, Local
Genomics
Mutation
Adult
Aged
Aged, 80 and over
Middle Aged
Female
DNA Copy Number Variations
Whole Genome Sequencing
Developmental Biology
11 Medical and Health Sciences
06 Biological Sciences
Publication Status: Published
Appears in Collections:Division of Surgery
Division of Cancer
Faculty of Medicine



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