AI Article Synopsis
- High-grade serous ovarian carcinoma (HGSOC) has a poor prognosis and is linked to significant chromosome instability (CIN), making it a challenging cancer to treat.
- This study examined 287 HGSOC tissue samples and 73 cell line models, revealing that centrosome amplification (CA) through centriole overduplication is a common and variable characteristic of HGSOC.
- High levels of CA in ovarian cancer cell lines correlate with increased resistance to treatments, especially paclitaxel, suggesting that CA may drive tumor evolution and serve as a valuable biomarker for treatment response.
Article 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.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC10579337 | PMC |
| http://dx.doi.org/10.1038/s41467-023-41840-3 | DOI Listing |
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