Evidence map›Paper›PMID 24816255›Full record

ArticleNature genetics2014

Recurrent gain-of-function mutations of RHOA in diffuse-type gastric carcinoma.

Miwako Kakiuchi, Takashi Nishizawa, Hiroki Ueda, Kengo Gotoh, Atsushi Tanaka, Akimasa Hayashi, Shogo Yamamoto, Kenji Tatsuno, Hiroto Katoh, Yoshiaki Watanabe and 12 more

Abstract read
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In one paragraph

Article in Nature genetics, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 314 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
314citing papers in PubMed, 1 pooled it
37.0field-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

314 citing papers in PubMed, 1 synthesis or guideline pooled it, 504 citations in OpenAlex.

  1. Pooled it
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  12. Decoding Rho GTPase signalling networks in directed cell migration.Frontiers in cell and developmental biology · 2026
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254 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

22 authors at 3 institutions in 1 country.

Miwako Kakiuchi1] Genome Science Division, Research Center for Advanced Science and Technology, The University of Tokyo, Tokyo, Japan. [2] Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
Takashi NishizawaForerunner Pharma Research Co., Ltd., Tokyo, Japan.
Hiroki UedaGenome Science Division, Research Center for Advanced Science and Technology, The University of Tokyo, Tokyo, Japan.
Kengo GotohGenome Science Division, Research Center for Advanced Science and Technology, The University of Tokyo, Tokyo, Japan.
Atsushi TanakaDepartment of Pathology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
Akimasa HayashiDepartment of Pathology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
Shogo Yamamoto1] Genome Science Division, Research Center for Advanced Science and Technology, The University of Tokyo, Tokyo, Japan. [2] Translational Systems Biology and Medicine Initiative (TSBMI), The University of Tokyo, Tokyo, Japan.
Kenji Tatsuno1] Genome Science Division, Research Center for Advanced Science and Technology, The University of Tokyo, Tokyo, Japan. [2] Translational Systems Biology and Medicine Initiative (TSBMI), The University of Tokyo, Tokyo, Japan.
Hiroto KatohDepartment of Genomic Pathology, Medical Research Institute, Tokyo Medical and Dental University, Tokyo, Japan.
Yoshiaki WatanabeKamakura Research Laboratories, Chugai Pharmaceutical Co., Ltd., Kanagawa, Japan.
Takashi IchimuraDepartment of Pathology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
Tetsuo UshikuDepartment of Pathology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
Shinichi FunahashiForerunner Pharma Research Co., Ltd., Tokyo, Japan.
Keisuke TateishiDepartment of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
Ikuo WadaDepartment of Gastrointestinal Surgery, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
Nobuyuki ShimizuDepartment of Gastrointestinal Surgery, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
Sachiyo NomuraDepartment of Gastrointestinal Surgery, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
Kazuhiko KoikeDepartment of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
Yasuyuki SetoDepartment of Gastrointestinal Surgery, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
Masashi FukayamaDepartment of Pathology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
Hiroyuki Aburatani1] Genome Science Division, Research Center for Advanced Science and Technology, The University of Tokyo, Tokyo, Japan. [2] Translational Systems Biology and Medicine Initiative (TSBMI), The University of Tokyo, Tokyo, Japan.
Shumpei Ishikawa1] Genome Science Division, Research Center for Advanced Science and Technology, The University of Tokyo, Tokyo, Japan. [2] Department of Pathology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan. [3] Department of Genomic Pathology, Medical Research Institute, Tokyo Medical and Dental University, Tokyo, Japan.
The University of Tokyo · JPTokyo Medical and Dental University · JPSystems Biology Institute · JP

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Diffuse-type gastric carcinoma (DGC) is characterized by a highly malignant phenotype with prominent infiltration and stromal induction. We performed whole-exome sequencing on 30 DGC cases and found recurrent RHOA nonsynonymous mutations. With validation sequencing of an additional 57 cases, RHOA mutation was observed in 25.3% (22/87) of DGCs, with mutational hotspots affecting the Tyr42, Arg5 and Gly17 residues in RHOA protein. These positions are highly conserved among RHO family members, and Tyr42 and Arg5 are located outside the guanine nucleotide-binding pocket. Several lines of functional evidence indicated that mutant RHOA works in a gain-of-function manner. Comparison of mutational profiles for the major gastric cancer subtypes showed that RHOA mutations occur specifically in DGCs, the majority of which were histopathologically characterized by the presence of poorly differentiated adenocarcinomas together with more differentiated components in the gastric mucosa. Our findings identify a potential therapeutic target for this poor-prognosis subtype of gastric cancer with no available molecularly targeted drugs.

Indexed as

MutationAdenocarcinomaAmino Acid SequenceCarcinomaCell DifferentiationDNA Mutational AnalysisGastric MucosaGene LibraryGerm-Line MutationHigh-Throughput Nucleotide SequencingHumansModels, MolecularMolecular Sequence DataPhenotypePrognosisrhoA GTP-Binding ProteinrhoA GTP-Binding ProteinRHOA protein, humanRNA, Small Interfering

Identifiers

PMID24816255
OpenAlexW1965619419

What OpenQuestion holds

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Registered trials

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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.