Evidence map›Paper›PMID 25625625›Full record

ArticleNature communications2015

Coexistent ARID1A-PIK3CA mutations promote ovarian clear-cell tumorigenesis through pro-tumorigenic inflammatory cytokine signalling.

Ronald L Chandler, Jeffrey S Damrauer, Jesse R Raab, Jonathan C Schisler, Matthew D Wilkerson, John P Didion, Joshua Starmer, Daniel Serber, Della Yee, Jessie Xiong and 4 more

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Nature communications, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 193 papers.

0numbers the graph read from it
0cells of the map it votes in
193citing papers in PubMed
15.2field-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.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

193 citing papers in PubMed, 315 citations in OpenAlex.

  1. Phase II Study of Copanlisib in Patients With Tumors WithJournal of clinical oncology : official journal of the American Society of Clinical Oncology · 2022
    Trial
  2. Phase II Trial and Correlative Genomic Analysis of Everolimus Plus Bevacizumab in Advanced Non-Clear Cell Renal Cell Carcinoma.Journal of clinical oncology : official journal of the American Society of Clinical Oncology · 2016
    Trial
  3. Article
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  11. The cross-talk between GSK-3β, RKIP, and PTEN as potential targets for therapeutic implications in cancer: a comprehensive insight.Journal of pharmacy & pharmaceutical sciences : a publication of the Canadian Society for Pharmaceutical Sciences, Societe canadienne des sciences pharmaceutiques · 2026
    Review
  12. Article
  13. Review
  14. A case of primary ovarian clear cell carcinoma withInternational cancer conference journal · 2025
    Article
  15. Review
  16. Article
  17. Article
  18. Article
  19. Article
  20. Article

133 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

14 authors at 1 institution in 1 country.

Ronald L Chandler1] Department of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, USA [2] Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, USA.
Jeffrey S Damrauer1] Department of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, USA [2] Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, USA.
Jesse R Raab1] Department of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, USA [2] Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, USA.
Jonathan C Schisler1] McAllister Heart Institute, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, USA [2] Department of Pharmacology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, USA.
Matthew D Wilkerson1] Department of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, USA [2] Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, USA.
John P Didion1] Department of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, USA [2] Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, USA.
Joshua Starmer1] Department of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, USA [2] Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, USA.
Daniel Serber1] Department of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, USA [2] Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, USA.
Della Yee1] Department of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, USA [2] Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, USA.
Jessie XiongLineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, USA.
David B DarrLineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, USA.
Fernando Pardo-Manuel de Villena1] Department of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, USA [2] Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, USA.
William Y Kim1] Department of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, USA [2] Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, USA [3] Department of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, USA.
Terry Magnuson1] Department of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, USA [2] Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, USA.
University of North Carolina at Chapel Hill · US

Funding

Pre-doctoral Training Program in Integrative Vascular BiologyT32HL069768 · NHLBI · UNIV OF NORTH CAROLINA CHAPEL HILL · PI Christopher P. Mack · 2002 to 2026
$9.7M
GENETIC REGULATION OF MURINE PLACENTAL DEVELOPMENTR01HD036655 · NICHD · UNIV OF NORTH CAROLINA CHAPEL HILL · PI MAGNUSON, TERRY R · 1999 to 2018
$5.2M
Characterization and therapeutic targeting of HIF in LKB1 - deficient lung cancerR01CA142794 · NCI · UNIV OF NORTH CAROLINA CHAPEL HILL · PI KIM, WILLIAM Y. · 2010 to 2014
$1.5M
Linking DNA Replication Origin Licensing with Cell Cycle ProgressionF31CA165891 · NCI · UNIV OF NORTH CAROLINA CHAPEL HILL · PI COLEMAN, KATE E · 2013 to 2015
$85k
NCI NIH HHS CA142794NCI NIH HHS R01 CA142794NHLBI NIH HHS T32 HL069768NHLBI NIH HHS T32-HL069768NICHD NIH HHS HD03665NICHD NIH HHS R01 HD036655
6 · The paper itself

Abstract

Ovarian clear-cell carcinoma (OCCC) is an aggressive form of ovarian cancer with high ARID1A mutation rates. Here we present a mutant mouse model of OCCC. We find that ARID1A inactivation is not sufficient for tumour formation, but requires concurrent activation of the phosphoinositide 3-kinase catalytic subunit, PIK3CA. Remarkably, the mice develop highly penetrant tumours with OCCC-like histopathology, culminating in haemorrhagic ascites and a median survival period of 7.5 weeks. Therapeutic treatment with the pan-PI3K inhibitor, BKM120, prolongs mouse survival by inhibiting the tumour cell growth. Cross-species gene expression comparisons support a role for IL-6 inflammatory cytokine signalling in OCCC pathogenesis. We further show that ARID1A and PIK3CA mutations cooperate to promote tumour growth through sustained IL-6 overproduction. Our findings establish an epistatic relationship between SWI/SNF chromatin remodelling and PI3K pathway mutations in OCCC and demonstrate that these pathways converge on pro-tumorigenic cytokine signalling. We propose that ARID1A protects against inflammation-driven tumorigenesis.

Indexed as

Adenocarcinoma, Clear CellAllelesAnimalsCarcinogenesisCell ProliferationCell SurvivalClass I Phosphatidylinositol 3-KinasesCytokinesDNA-Binding ProteinsEnzyme ActivationFemaleGenes, Tumor SuppressorHaploinsufficiencyInflammationInterleukin-6Mice, Inbred C57BLArid1a protein, mouseClass I Phosphatidylinositol 3-KinasesCytokinesDNA-Binding ProteinsInterleukin-6Nuclear ProteinsPhosphatidylinositol 3-KinasesPhosphoinositide-3 Kinase InhibitorsPik3ca protein, mouseProtein Kinase InhibitorsTranscription Factors

Identifiers

PMID25625625
PMCPMC4308813
OpenAlexW1978088642

What OpenQuestion holds

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Registered trials

None linked

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.