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Endometrioid ovarian carcinoma (EnOC) demonstrates substantial clinical and molecular heterogeneity. Here, we report whole exome sequencing of 112 EnOC cases following rigorous pathological assessment. We detect a high frequency of mutation in CTNNB1(43%), PIK3CA(43%), ARID1A(36%), PTEN(29%), TP53(26%) and SOX8(19%), a recurrently-mutated gene previously unreported in EnOC. POLE and mismatch repair protein-encoding genes were mutated at lower frequency (6%, 18%) with significant co-occurrence. A molecular taxonomy is constructed, identifying clinically distinct EnOC subtypes: cases with TP53 mutation demonstrate greater genomic complexity, are commonly FIGO stage III/IV at diagnosis (48%), are frequently incompletely debulked (44%) and demonstrate inferior survival; conversely, cases with CTNNB1 mutation, which is mutually exclusive with TP53 mutation, demonstrate low genomic complexity and excellent clinical outcome, and are predominantly stage I/II at diagnosis (89%) and completely resected (87%). Moreover, we identify the WNT, MAPK/RAS and PI3K pathways as good candidate targets for molecular therapeutics in EnOC.
|Early online date||5 Oct 2020|
|Publication status||E-pub ahead of print - 5 Oct 2020|
- ovarian carcinoma
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C Simon Herrington
- Deanery of Molecular, Genetic and Population Health Sciences - Chair of Molecular Pathology of Cancer
- Edinburgh Pathology
- Edinburgh Cancer Research Centre
Person: Academic: Research Active