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Molecular stratification of endometrioid ovarian carcinoma predicts clinical outcome
- Source :
- Nature Communications, Nature Communications, Vol 11, Iss 1, Pp 1-10 (2020), Hollis, R, Thomson, J, Stanley, B, Churchman, M, Meynert, A M, Rye, T, Bartos, C, Iida, Y, Croy, I, Mackean, M J, Nussey, F, Okamoto, A, Semple, C A, Gourley, C & Herrington, C S 2020, ' Molecular stratification of endometrioid ovarian carcinoma predicts clinical outcome ', Nature Communications, vol. 11, no. 10, 4995 . https://doi.org/10.1038/s41467-020-18819-5
- Publication Year :
- 2020
- Publisher :
- Cold Spring Harbor Laboratory, 2020.
-
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.<br />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.
- Subjects :
- 0301 basic medicine
Oncology
stratificatioon
ARID1A
General Physics and Astronomy
medicine.disease_cause
genomic
0302 clinical medicine
Ovarian carcinoma
Stage (cooking)
lcsh:Science
Exome sequencing
Cancer
Aged, 80 and over
Ovarian Neoplasms
Mutation
Multidisciplinary
biology
Middle Aged
Prognosis
030220 oncology & carcinogenesis
Female
Microsatellite Instability
DNA mismatch repair
Carcinoma, Endometrioid
Signal Transduction
Adult
medicine.medical_specialty
DNA Copy Number Variations
Science
survival
General Biochemistry, Genetics and Molecular Biology
Article
03 medical and health sciences
Ovarian cancer
Internal medicine
Exome Sequencing
Carcinoma
Biomarkers, Tumor
medicine
cancer
Humans
PTEN
molecular
Pathological
Aged
Gynaecological cancer
business.industry
Microsatellite instability
General Chemistry
medicine.disease
ovarian carcinoma
030104 developmental biology
biology.protein
lcsh:Q
business
endometrioid
Subjects
Details
- Database :
- OpenAIRE
- Journal :
- Nature Communications, Nature Communications, Vol 11, Iss 1, Pp 1-10 (2020), Hollis, R, Thomson, J, Stanley, B, Churchman, M, Meynert, A M, Rye, T, Bartos, C, Iida, Y, Croy, I, Mackean, M J, Nussey, F, Okamoto, A, Semple, C A, Gourley, C & Herrington, C S 2020, ' Molecular stratification of endometrioid ovarian carcinoma predicts clinical outcome ', Nature Communications, vol. 11, no. 10, 4995 . https://doi.org/10.1038/s41467-020-18819-5
- Accession number :
- edsair.doi.dedup.....ee15956b2f6f9f31f51e9c9b2fe0e8a6