Genetic heterogeneity and evolutionary history of high-grade ovarian carcinoma and matched distant metastases.
Br J Cancer
; 122(8): 1219-1230, 2020 04.
Article
em En
| MEDLINE
| ID: mdl-32099096
ABSTRACT
BACKGROUND:
High-grade serous ovarian carcinoma (HGSOC) is the most frequent type of ovarian carcinoma, associated with poor clinical outcome and metastatic disease. Although metastatic processes are becoming more understandable, the genomic landscape and metastatic progression in HGSOC has not been elucidated.METHODS:
Multi-region whole-exome sequencing was performed on HGSOC primary tumours and their metastases (n = 33 tumour regions) from six patients. The resulting somatic variants were analysed to delineate tumour evolution and metastatic dissemination, and to compare the repertoire of events between primary HGSOC and metastasis.RESULTS:
All cases presented branching evolution patterns in primary HGSOC, with three cases further showing parallel evolution in which different mutations on separate branches of a phylogenetic tree converge on the same gene. Furthermore, linear metastatic progression was observed in 67% of cases with late dissemination, in which the metastatic tumour mostly acquires the same mutational process active in primary tumour, and parallel metastatic progression, with early dissemination in the remaining 33.3% of cases. Metastatic-specific SNVs were further confirmed as late dissemination events. We also found the involvement of metastatic-specific driver events in the Wnt/ß-catenin pathway, and identified potential clinically actionable events in individual patients of the metastatic HGSOC cohort.CONCLUSIONS:
This study provides deeper insights into clonal evolution and mutational processes that can pave the way to new therapeutic targets.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Neoplasias Ovarianas
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Cistadenocarcinoma Seroso
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Heterogeneidade Genética
Tipo de estudo:
Etiology_studies
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Incidence_studies
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Observational_studies
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Prognostic_studies
/
Risk_factors_studies
Limite:
Adult
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Female
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Humans
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Middle aged
Idioma:
En
Ano de publicação:
2020
Tipo de documento:
Article