Molecular stratification of endometrioid ovarian carcinoma predicts clinical outcome
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%), K...
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Published in | Nature communications Vol. 11; no. 1; p. 4995 |
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Main Authors | , , , , , , , , , , , , , , |
Format | Journal Article |
Language | English |
Published |
London
Nature Publishing Group UK
05.10.2020
Nature Publishing Group Nature Portfolio |
Subjects | |
Online Access | Get full text |
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Summary: | 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.
The molecular classification of endometroid ovarian carcinomas (EnOC) has not been established, preventing the development of stratified therapeutic approaches. Here the authors characterise the molecular landscape of EnOC by whole exome sequencing, identifying clinically distinct disease subtypes. |
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Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 |
ISSN: | 2041-1723 2041-1723 |
DOI: | 10.1038/s41467-020-18819-5 |