Molecular stratification of endometrioid ovarian carcinoma predicts clinical outcome

Endometrioid ovarian carcinoma (EnOC) is an under-investigated type of ovarian carcinoma. Here, we report the largest genomic study of EnOCs to date, performing whole exome sequencing of 112 cases following rigorous pathological assessment. High frequencies of mutation were detected in CTNNB1(43%), PIK3CA(43%), ARID1A(36%), PTEN(29%), TP53(26%) and SOX8(19%), a novel target of recurrent mutation in EnOC. POLE and mismatch repair protein-encoding genes were mutated at lower frequency (6%, 18%) with significant co-occurrence. A molecular taxonomy was constructed using a novel algorithm (PRISTINE), identifying clinically distinct EnOC subtypes: TP53m cases demonstrated greater genomic complexity, were frequently FIGO stage III/IV at diagnosis (48%) and incompletely debulked (44%), and demonstrated inferior survival; conversely, CTNNB1m cases demonstrated low complexity and excellent clinical outcome, were predominantly stage I/II at diagnosis (89%) and completely resected (87%). Tumour complexity provides further resolution within the TP53wt/CTNNB1wt group. Moreover, we identify the WNT, MAPK/RAS and PI3K pathways as good candidate targets for molecular therapeutics in EnOC.

Type: Other
Archiver: European Genome-Phenome Archive (EGA)

1 Dataset 2 Publications

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Dataset ID	Description	Technology	Samples
EGAD00001006389	Whole Exome sequencing data of tumour samples for 112 patients with endometrioid ovarian carcinoma in FASTQ format. Data was derived as summarized below: Library Preparation: Libraries were prepared from each DNA sample using the Illumina TruSeq Exome Library Prep kit (#FC-150-1002) according to the provided protocol using modifications for working with FFPE sourced material. Libraries were quantified using the Qubit 2.0 Fluorometer and the Qubit DNA HS assay (#Q32854) and the size distribution of fragments was assessed using the Agilent Bioanalyser with the DNA HS Kit (#5067-4626). Library QC: Exome-captured sequencing library pools were quantified using the Qubit 2.0 Fluorometer and the Qubit DNA HS assay (#Q32854) and the size distribution of fragments was assessed using the Agilent Bioanalyser with the DNA HS Kit (#5067-4626). Fragment size and quantity measurements were used to calculate molarity for each library pool. Sequencing: Sequencing was performed using the NextSeq 500/550 High-Output v2 (150 cycle) Kit (# FC-404-2002) on the NextSeq 550 platform (Illumina Inc, #SY-415-1002).	NextSeq 550	112

Publications	Citations
Molecular stratification of endometrioid ovarian carcinoma predicts clinical outcome. Hollis RL, Thomson JP, Stanley B, Churchman M, Meynert AM, Rye T, Bartos C, Iida Y, Croy I, Mackean M, Nussey F, Okamoto A, Semple CA, Gourley C, Herrington CS. Nat Commun 11: 2020 4995	52
Integrated molecular characterisation of endometrioid ovarian carcinoma identifies opportunities for stratification. Hollis RL, Stanley B, Thomson JP, Churchman M, Croy I, Rye T, Bartos C, Nussey F, Mackean M, Meynert AM, Semple CA, Gourley C, Herrington CS. NPJ Precis Oncol 5: 2021 47	12