ArticlePLoS genetics2014
Germline mutations in MAP3K6 are associated with familial gastric cancer.
Article in PLoS genetics, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
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Who cites it
35 citing papers in PubMed, 68 citations in OpenAlex.
- Multigene Germline Panel Testing in Gastric Cancer Patients in a Portuguese Population.Cancer medicine · 2026Observational
- Review
- Germline variants in CDKN2A wild-type melanoma prone families.Molecular oncology · 2025Article
- Exploring MAP3K genes in gastric cancer: biomarkers, tumor microenvironment dynamics, and chemotherapy resistance.Hereditas · 2025Article
- Confocal endomicroscopy diagnostic criteria for early signet-ring cell carcinoma in hereditary diffuse gastric cancer.BMC gastroenterology · 2023Article
- Article
- Hereditary Diffuse Gastric Cancer: A 2022 Update.Journal of personalized medicine · 2022Review
- Landscape of Druggable Molecular Pathways Downstream of Genomic CDH1/Cadherin-1 Alterations in Gastric Cancer.Journal of personalized medicine · 2022Article
- Article
- Hydrogen inhibits the proliferation and migration of gastric cancer cells by modulating lncRNA MALAT1/miR-124-3p/EZH2 axis.Cancer cell international · 2021Article
- Increased risk for uterine cancer among first-degree relatives to Swedish gastric cancer patients.Hereditary cancer in clinical practice · 2020Article
- Diffuse gastric cancer: histologic, molecular, and genetic basis of disease.Translational gastroenterology and hepatology · 2020Review
- Multigene Panel Testing Increases the Number of Loci Associated with Gastric Cancer Predisposition.Cancers · 2019Article
- Frequency of CDH1 germline variants and contribution of dietary habits in early age onset gastric cancer patients in Brazil.Gastric cancer : official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association · 2019Article
- The role of endoscopy in the management of hereditary diffuse gastric cancer syndrome.World journal of gastroenterology · 2019Review
- Clinical spectrum and pleiotropic nature ofJournal of medical genetics · 2019Review
- Role of germline aberrations affectingJournal of medical genetics · 2018Article
- Diffuse Gastric Cancer: A Summary of Analogous Contributing Factors for Its Molecular Pathogenicity.International journal of molecular sciences · 2018Review
- Germline mutations in hereditary diffuse gastric cancer.Chinese journal of cancer research = Chung-kuo yen cheng yen chiu · 2018Article
- Comparative study of endoscopic surveillance in hereditary diffuse gastric cancer according to CDH1 mutation status.Gastrointestinal endoscopy · 2018Article
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Authors and funding
26 authors at 6 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Gastric cancer is among the leading causes of cancer-related deaths worldwide. While heritable forms of gastric cancer are relatively rare, identifying the genes responsible for such cases can inform diagnosis and treatment for both hereditary and sporadic cases of gastric cancer. Mutations in the E-cadherin gene, CDH1, account for 40% of the most common form of familial gastric cancer (FGC), hereditary diffuse gastric cancer (HDGC). The genes responsible for the remaining forms of FGC are currently unknown. Here we examined a large family from Maritime Canada with FGC without CDH1 mutations, and identified a germline coding variant (p.P946L) in mitogen-activated protein kinase kinase kinase 6 (MAP3K6). Based on conservation, predicted pathogenicity and a known role of the gene in cancer predisposition, MAP3K6 was considered a strong candidate and was investigated further. Screening of an additional 115 unrelated individuals with non-CDH1 FGC identified the p.P946L MAP3K6 variant, as well as four additional coding variants in MAP3K6 (p.F849Sfs*142, p.P958T, p.D200Y and p.V207G). A somatic second-hit variant (p.H506Y) was present in DNA obtained from one of the tumor specimens, and evidence of DNA hypermethylation within the MAP3K6 gene was observed in DNA from the tumor of another affected individual. These findings, together with previous evidence from mouse models that MAP3K6 acts as a tumor suppressor, and studies showing the presence of somatic mutations in MAP3K6 in non-hereditary gastric cancers and gastric cancer cell lines, point towards MAP3K6 variants as a predisposing factor for FGC.
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