Evidence map›Paper›PMID 31857578›Full record

Observational studyNature communications2019

Uterine adenomyosis is an oligoclonal disorder associated with KRAS mutations.

Satoshi Inoue, Yasushi Hirota, Toshihide Ueno, Yamato Fukui, Emiko Yoshida, Takuo Hayashi, Shinya Kojima, Reina Takeyama, Taiki Hashimoto, Tohru Kiyono and 14 more

Registry-linked trialOpen access · goldAbstract readObservational Study
In one paragraph

Observational study in Nature communications, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT06289257 (Analysis of Vitamin D and VDR Expression in Women With Advanced Endometriosis), which is not on this map. Cited by 73 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
73citing papers in PubMed, 2 pooled it
17.1field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

NCT06289257 completednot on this mapstarted 2024, after this paper: background citation

Analysis of Vitamin D and VDR Expression in Women With Advanced Endometriosis: A Case-Control Study in Thailand

Typeobservational_patient_registrySponsorKhon Kaen UniversityRan2024 to 2024Enrolled108ConditionsEndometriosis, Vitamin D Deficiency/Insufficiency, Vitamin D StatusArmsVitamin D level, Vitamin D receptor
3 · Its place in the literature

Who cites it

73 citing papers in PubMed, 2 syntheses or guidelines pooled it, 131 citations in OpenAlex.

  1. Pooled it
  2. Adenomyosis as a Risk Factor for Myometrial or Endometrial Neoplasms-Review.International journal of environmental research and public health · 2022
    Pooled it
  3. Article
  4. Review
  5. Building Disease Models for Endometriosis: iPSCs as Game-Changers.International journal of molecular sciences · 2026
    Review
  6. Article
  7. Review
  8. Article
  9. Review
  10. Article
  11. Review
  12. Article
  13. Article
  14. Article
  15. Article
  16. Article
  17. Mutation profile and chromosomal abnormality in adenomyosis.Reproduction (Cambridge, England) · 2025
    Article
  18. Review
  19. Article
  20. Article

13 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

24 authors at 6 institutions in 2 countries.

Satoshi InoueDepartment of Medical Genomics, The University of Tokyo, Tokyo, 113-0033, Japan. satoshiinouencc4@gmail.com.ORCID http://orcid.org/0000-0003-1484-2228
Yasushi HirotaDepartment of Obstetrics and Gynecology, The University of Tokyo, Tokyo, 113-0033, Japan.ORCID http://orcid.org/0000-0003-0241-9780
Toshihide UenoDivision of Cellular Signaling, National Cancer Center Research Institute, Tokyo, 104-0045, Japan.ORCID http://orcid.org/0000-0002-7408-7298
Yamato FukuiDepartment of Obstetrics and Gynecology, The University of Tokyo, Tokyo, 113-0033, Japan.
Emiko YoshidaDepartment of Obstetrics and Gynecology, Juntendo University Faculty of Medicine, Tokyo, 113-8421, Japan.
Takuo HayashiDepartment of Human Pathology, Juntendo University Faculty of Medicine, Tokyo, 113-8421, Japan.
Shinya KojimaDivision of Cellular Signaling, National Cancer Center Research Institute, Tokyo, 104-0045, Japan.
Reina TakeyamaDivision of Cellular Signaling, National Cancer Center Research Institute, Tokyo, 104-0045, Japan.
Taiki HashimotoDivision of Diagnostic Pathology, National Cancer Center Hospital, Tokyo, 104-0045, Japan.ORCID http://orcid.org/0000-0003-3148-9243
Tohru KiyonoDivision of Carcinogenesis and Cancer Prevention, and Department of Cell Culture Technology, National Cancer Center Research Institute, Tokyo, 104-0045, Japan.ORCID http://orcid.org/0000-0003-1769-403X
Masako IkemuraDepartment of Pathology, Graduate School of Medicine, The University of Tokyo, Tokyo, 113-0033, Japan.
Ayumi TaguchiDepartment of Obstetrics and Gynecology, The University of Tokyo, Tokyo, 113-0033, Japan.ORCID http://orcid.org/0000-0002-5491-3871
Tomoki TanakaDepartment of Obstetrics and Gynecology, The University of Tokyo, Tokyo, 113-0033, Japan.
Yosuke TanakaDivision of Cellular Signaling, National Cancer Center Research Institute, Tokyo, 104-0045, Japan.
Seiji SakataPathology Project for Molecular Targets, The Cancer Institute, Japanese Foundation for Cancer Research, Tokyo, 135-8550, Japan.
Kengo TakeuchiPathology Project for Molecular Targets, The Cancer Institute, Japanese Foundation for Cancer Research, Tokyo, 135-8550, Japan.ORCID http://orcid.org/0000-0002-1599-5800
Ayako MuraokaDepartment of Obstetrics and Gynecology, Nagoya University Graduate School of Medicine, Nagoya, 466-8550, Japan.
Satoko OsukaDepartment of Obstetrics and Gynecology, Nagoya University Graduate School of Medicine, Nagoya, 466-8550, Japan.
Tsuyoshi SaitoDepartment of Human Pathology, Juntendo University Faculty of Medicine, Tokyo, 113-8421, Japan.
Katsutoshi OdaDepartment of Obstetrics and Gynecology, The University of Tokyo, Tokyo, 113-0033, Japan.
Yutaka OsugaDepartment of Obstetrics and Gynecology, The University of Tokyo, Tokyo, 113-0033, Japan.
Yasuhisa TeraoDepartment of Obstetrics and Gynecology, Juntendo University Faculty of Medicine, Tokyo, 113-8421, Japan.ORCID http://orcid.org/0000-0002-9126-3361
Masahito KawazuDepartment of Medical Genomics, The University of Tokyo, Tokyo, 113-0033, Japan.
Hiroyuki ManoDivision of Cellular Signaling, National Cancer Center Research Institute, Tokyo, 104-0045, Japan.
The University of Tokyo · JPJuntendo University · JPJapanese Foundation For Cancer Research · JPNagoya University · JPTokyo Medical University · JPTokyo National Hospital · JP

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Uterine adenomyosis is a benign disorder that often co-occurs with endometriosis and/or leiomyoma, and impairs quality of life. The genomic features of adenomyosis are unknown. Here we apply next-generation sequencing to adenomyosis (70 individuals and 192 multi-regional samples), as well as co-occurring leiomyoma and endometriosis, and find recurring KRAS mutations in 26/70 (37.1%) of adenomyosis cases. Multi-regional sequencing reveals oligoclonality in adenomyosis, with some mutations also detected in normal endometrium and/or co-occurring endometriosis. KRAS mutations are more frequent in cases of adenomyosis with co-occurring endometriosis, low progesterone receptor (PR) expression, or progestin (dienogest; DNG) pretreatment. DNG's anti-proliferative effect is diminished via epigenetic silencing of PR in immortalized cells with mutant KRAS. Our genomic analyses suggest that adenomyotic lesions frequently contain KRAS mutations that may reduce DNG efficacy, and that adenomyosis and endometriosis may share molecular etiology, explaining their co-occurrence. These findings could lead to genetically guided therapy and/or relapse risk assessment after uterine-sparing surgery.

Indexed as

AdenomyosisAdultCell ProliferationDNA Mutational AnalysisEndometriosisEndometriumFemaleHigh-Throughput Nucleotide SequencingHumansHysterectomyMiddle AgedMutationMyometriumNandroloneProto-Oncogene Proteins p21(ras)Receptors, ProgesteronedienogestKRAS protein, humanNandroloneProto-Oncogene Proteins p21(ras)Receptors, Progesterone

Identifiers

PMID31857578
PMCPMC6923389
OpenAlexW2996540178

What OpenQuestion holds

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LicenceCC BY
Read underepoch 390

Registered trials

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.