학술논문
Molecular landscape and functional characterization of centrosome amplification in ovarian cancer
Document Type
Original Paper
Author
Sauer, Carolin M.; Hall, James A.; Couturier, Dominique-Laurent; Bradley, Thomas; Piskorz, Anna M.; Griffiths, Jacob; Sawle, Ashley; Eldridge, Matthew D.; Smith, Philip; Hosking, Karen; Reinius, Marika A. V.; Morrill Gavarró, Lena; Mes-Masson, Anne-Marie; Ennis, Darren; Millan, David; Hoyle, Aoisha; McNeish, Iain A.; Jimenez-Linan, Mercedes; Martins, Filipe Correia; Tischer, Julia; Vias, Maria; Brenton, James D.
Source
Nature Communications. 14(1)
Subject
Language
English
ISSN
2041-1723
Abstract
High-grade serous ovarian carcinoma (HGSOC) is characterised by poor outcome and extreme chromosome instability (CIN). Therapies targeting centrosome amplification (CA), a key mediator of chromosome missegregation, may have significant clinical utility in HGSOC. However, the prevalence of CA in HGSOC, its relationship to genomic biomarkers of CIN and its potential impact on therapeutic response have not been defined. Using high-throughput multi-regional microscopy on 287 clinical HGSOC tissues and 73 cell lines models, here we show that CA through centriole overduplication is a highly recurrent and heterogeneous feature of HGSOC and strongly associated with CIN and genome subclonality. Cell-based studies showed that high-prevalence CA is phenocopied in ovarian cancer cell lines, and that high CA is associated with increased multi-treatment resistance; most notably to paclitaxel, the commonest treatment used in HGSOC. CA in HGSOC may therefore present a potential driver of tumour evolution and a powerful biomarker for response to standard-of-care treatment.
The prevalence of centrosome amplification (CA) and the genomic landscape of chromosomal instability in high-grade serous ovarian carcinoma (HGSOC) remain to be explored. Here the authors suggest CA as a potential driver of tumour evolution and a biomarker for treatment response in HGSOC.
The prevalence of centrosome amplification (CA) and the genomic landscape of chromosomal instability in high-grade serous ovarian carcinoma (HGSOC) remain to be explored. Here the authors suggest CA as a potential driver of tumour evolution and a biomarker for treatment response in HGSOC.