Whole exome sequencing of low grade serous ovarian carcinoma identifies genomic events associated with clinical outcome
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Le résumé fourni par la source
OBJECTIVES: Low-grade serous ovarian carcinoma (LGSOC) is a distinct, rare, ovarian cancer type characterised by younger patient age and intrinsic chemoresistance. Understanding the molecular landscape is crucial for optimising targeted therapy. METHODS: Genomic data from whole exome sequencing of tumour tissue was analysed in a LGSOC cohort with detailed clinical annotation. RESULTS: 63 cases were analysed and three subgroups identified based on single nucleotide variants: canonical MAPK mutant (cMAPKm: 52%, KRAS/BRAF/NRAS), MAPK-associated gene mutation (MAPK-assoc: 27%) and MAPK wild-type (MAPKwt: 21%). NOTCH pathway disruption occurred across all subgroups. Tumour mutational burden (TMB), mutational signatures and recurrent copy number (CN) changes varied across the cohort with co-occurrence of chromosome 1p loss and 1q gain (CN Chr1pq) a recurrent feature. Low TMB and CN Chr1pq were associated with inferior disease-specific survival (HR 6.43; p < 0.001 and HR 3.29, p = 0.011 respectively). Stepwise genomic classification in relation to outcome resulted in four groups (TMB low; CN Chr1pq; MAPKwt/MAPKassoc; cMAPKm). 5 year disease-specific survival was 46%, 55%, 79% and 100% respectively for these groups. The two most favourable genomic subgroups were enriched for the SBS10b mutational signature, particularly the cMAPKm subgroup. CONCLUSIONS: LGSOC comprises multiple genomic subgroups with distinct clinical and molecular features. Chr1pq CN arm disruption and TMB represent promising methods to identify individuals with poorer prognosis. Further investigation of the molecular basis for these observations is required. MAPKwt cases represent around a fifth of patients. NOTCH inhibitors represent a candidate therapeutic strategy worthy of exploration across these cases.
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Le contrôle bibliographique ouvert
DOI retrouvé dans Crossref DOI retrouvé ; titre concordant.
- Titre Crossref
- Whole exome sequencing of low grade serous ovarian carcinoma identifies genomic events associated with clinical outcome
- Date Crossref
- 01/07/2023
- Éditeur
- Elsevier BV
- Type
- journal-article
Ce recoupement confirme des métadonnées liées au DOI. Il ne confirme ni la méthode ni les conclusions de l’étude, et il ne compte pas comme une seconde source scientifique indépendante.
Où se fait cette recherche
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Edinburgh Cancer Research pays non établi dans la noticeStructure de recherche
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The Netherlands Cancer Institute Department of Gynaecologic Oncology and Department of Pathology pays non établi dans la noticeÉtablissement de santé
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Cancer Research UK pays non établi dans la noticeOrganisation à but non lucratif
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Cancer Research UK Scotland Institute pays non établi dans la noticeStructure de recherche
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Institute of Genetics and Cancer pays non établi dans la noticeStructure de recherche
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University of Edinburgh Institute of Genetics and Cancer pays non établi dans la noticeUniversité ou école supérieure
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NHS Lothian pays non établi dans la noticeÉtablissement de santé
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Western General Hospital Edinburgh Cancer Centre pays non établi dans la noticeÉtablissement de santé
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Amsterdam University Medical Centres Department of Gynaecologic Oncology and Department of Pathology pays non établi dans la noticeUniversité ou école supérieure
Edinburgh Cancer Research, Department of Gynaecologic Oncology and Department of Pathology — The Netherlands Cancer Institute et Cancer Research UK, avec 6 autres affiliations.
Une affiliation ne permet pas de déduire la nationalité d’un auteur.