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| Open AccessSingle-cell transcriptomic analysis highlights origin and pathological process of human endometrioid endometrial carcinoma
Many aspects of the tumourigenesis of endometrioid endometrial cancers (EEC) are still poorly understood. Here, the authors use single-cell transcriptomics to characterise EEC tumours and their microenvironment across different stages, and reveal potential cells of origin for EEC.
- Xiaojun Ren
- , Jianqing Liang
- & Xiaojun Chen
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Article
| Open AccessTertiary lymphoid structures critical for prognosis in endometrial cancer patients
Tertiary lymphoid structures (TLS) are associated with a reduced risk of cancer recurrence and improved response to immune checkpoint blockade in several tumor types. Here the authors identify L1CAM as a marker for mature TLS and show that the presence of TLS is associated with favorable prognosis in patients with endometrial cancer from the PORTEC-3 trial.
- Nanda Horeweg
- , Hagma H. Workel
- & Marco de Bruyn
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Article
| Open AccessSpatiotemporal dynamics of clonal selection and diversification in normal endometrial epithelium
Through regeneration, the endometrium accumulates somatic mutations that can lead to diseases like endometriosis and cancer. Here, the authors use genomics to analyse normal endometrial glands from different patient cohorts, detect rhizome structures with common clonal ancestors and infer clonal expansion dynamics.
- Manako Yamaguchi
- , Hirofumi Nakaoka
- & Takayuki Enomoto
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Article
| Open AccessDiagnostic accuracy of cytology for the detection of endometrial cancer in urine and vaginal samples
Postmenopausal bleeding can be an indication of endometrial cancer. Here, the authors combine cytology of urine and vaginal samples from women with postmenopausal bleeding and demonstrate that they can accurately predict endometrial cancer with a sensitivity of 91.7% and specificity of 88.8%.
- Helena O’Flynn
- , Neil A. J. Ryan
- & Emma J. Crosbie
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Article
| Open AccessUterine adenomyosis is an oligoclonal disorder associated with KRAS mutations
Uterine adenomyosis often co-occurs with endometriosis or leiomyoma, but little is known about its molecular underpinnings. Here, the authors show that KRAS mutations are frequent in this disease, which might reduce sensitivity to progestin treatment via epigenetic silencing of the progesterone receptor.
- Satoshi Inoue
- , Yasushi Hirota
- & Hiroyuki Mano
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Article
| Open AccessMitochondrial supercomplex assembly promotes breast and endometrial tumorigenesis by metabolic alterations and enhanced hypoxia tolerance
Cancer cells rely on mitochondrial respiration to satisfy their metabolic demands. Here the authors show that the mitochondrial supercomplex assembly factor COX7RP is abundantly expressed in breast and endometrial cancer cells and promotes tumor growth and hypoxia tolerance partially by altering levels of the tricarboxylic acid cycle intermediates.
- Kazuhiro Ikeda
- , Kuniko Horie-Inoue
- & Satoshi Inoue
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Article
| Open AccessARID1A and PI3-kinase pathway mutations in the endometrium drive epithelial transdifferentiation and collective invasion
PIK3CA mutations and ARID1A loss co-exist in endometrial neoplasms. Here, the authors show that these co-mutations drive gene expression profiles correlated with differential chromatin accessibility and ARID1A binding in the endometrial epithelium, resulting in partial EMT and myometrial invasion.
- Mike R. Wilson
- , Jake J. Reske
- & Ronald L. Chandler
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Article
| Open AccessA recurrent cancer-associated substitution in DNA polymerase ε produces a hyperactive enzyme
Somatic alterations in the exonuclease domain of DNA polymerase ɛ have been linked to the development of highly mutated cancers. Here, the authors report that a major consequence of the most common cancer-associated Polɛ variant is a dramatically increased DNA polymerase activity.
- Xuanxuan Xing
- , Daniel P. Kane
- & Polina V. Shcherbakova