Evidence map›Paper›PMID 38605661›Full record

ArticleCancer research and treatment2024

Identification of New Pathogenic Variants of Hereditary Diffuse Gastric Cancer.

Seung-Young Oh, Giyong Jang, Jaeryuk Kim, Kyoung-Yun Jeong, Hyun Myong Kim, Yoon Jin Kwak, Seong-Ho Kong, Do Joong Park, Hyuk-Joon Lee, Sung-Yup Cho and 2 more

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In one paragraph

Article in Cancer research and treatment, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
1.4field-weighted citation impact, top 20% 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

2 citing papers in PubMed, 6 citations in OpenAlex.

  1. Hereditary diffuse gastric cancer: the evolution of a cancer syndrome.Journal of the Royal Society of New Zealand · 2025
    Review
  2. Review
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

12 authors at 4 institutions in 3 countries.

Seung-Young OhDepartment of Surgery, Seoul National University College of Medicine, Seoul, Korea.
Giyong JangGenomic Medicine Institute, Medical Research Center, Seoul National University, Seoul, Korea.
Jaeryuk KimGenomic Medicine Institute, Medical Research Center, Seoul National University, Seoul, Korea.
Kyoung-Yun JeongCancer Research Institute, Seoul National University, Seoul, Korea.
Hyun Myong KimCancer Research Institute, Seoul National University, Seoul, Korea.
Yoon Jin KwakDepartment of Pathology, Seoul National University College of Medicine, Seoul, Korea.
Seong-Ho KongDepartment of Surgery, Seoul National University College of Medicine, Seoul, Korea.
Do Joong ParkDepartment of Surgery, Seoul National University College of Medicine, Seoul, Korea.
Hyuk-Joon LeeDepartment of Surgery, Seoul National University College of Medicine, Seoul, Korea.
Sung-Yup ChoDepartment of Biomedical Sciences, Seoul National University College of Medicine, Seoul, Korea.
Jong-Il KimGenomic Medicine Institute, Medical Research Center, Seoul National University, Seoul, Korea.
Han-Kwang YangDepartment of Surgery, Seoul National University College of Medicine, Seoul, Korea.
Seoul National University · KRSeoul National University Hospital · KRNew Generation University College · ETBiomedical Research Institute · US

Funding

Ministry of EducationMinistry of Science and ICTNational Research Foundation of Korea 2021R1A2C3008021National Research Foundation of Korea RS-2023-00240042Seoul National University Hospital 05-2017-0010
6 · The paper itself

Abstract

purposeHereditary diffuse gastric cancer (HDGC) presents a significant genetic predisposition, notably linked to mutations in the CDH1 and CTNNA1. However, the genetic basis for over half of HDGC cases remains unidentified. The aim of this study is to identify novel pathogenic variants in HDGC and evaluate their protein expression. MATERIALS AND

methodsAmong 20 qualifying families, two were selected based on available pedigree and DNA. Whole genome sequencing (WGS) on DNA extracted from blood and whole exome sequencing on DNA from formalin-fixed paraffin-embedded tissues were performed to find potential pathogenic variants in HDGC. After selection of a candidate variant, functional validation, and enrichment analysis were performed.

resultsAs a result of WGS, three candidate germline mutations (EPHA5, MCOA2, and RHOA) were identified in one family. After literature review and in-silico analyses, the RHOA mutation (R129W) was selected as a candidate. This mutation was found in two gastric cancer patients within the family. In functional validation, it showed RhoA overexpression and a higher GTP-bound state in the RhoaR129W mutant. Decreased phosphorylation at Ser127/397 suggested altered YAP1 regulation in the Rho-ROCK pathway. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses linked RhoaR129W overexpression to changed migration/adhesion in MKN1 cell line. However, this RHOA mutation (R129W) was not found in index patients in other families.

conclusionThe RHOA mutation (R129W) emerges as a potential causative gene for HDGC, but only in one family, indicating a need for further studies to understand its role in HDGC pathogenesis fully.

Indexed as

Genetic Predisposition to DiseaseGerm-Line MutationPedigreeStomach NeoplasmsAdultExome SequencingFemaleHumansMaleMiddle AgedrhoA GTP-Binding ProteinWhole Genome SequencingrhoA GTP-Binding ProteinRHOA protein, humanFamilial gastric cancerGerm-line mutationHereditary diffuse gastric cancerPathogenic variantRHOA

Identifiers

PMID38605661
PMCPMC11491241
OpenAlexW4394719772

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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.