Molecular Stratification of Endometrioid Ovarian Carcinoma Predicts Clinical Outcome

Overview

Journal Nat Commun

Specialty Biology

Date 2020 Oct 6

PMID 33020491

Citations 51

Authors

Robert L Hollis

John P Thomson

Barbara Stanley

Michael Churchman

Alison M Meynert

Tzyvia Rye

Clare Bartos

Yasushi Iida

Ian Croy

Melanie Mackean

Fiona Nussey

Aikou Okamoto

Colin A Semple

Charlie Gourley

C Simon Herrington

Affiliations

Soon will be listed here.

Abstract

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%), KRAS (26%), 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.

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