ArticleGastroenterology2014
Germline mutations in oncogene-induced senescence pathways are associated with multiple sessile serrated adenomas.
Article in Gastroenterology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 75 papers, 3 of them syntheses that pooled it.
What it found
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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.
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Who cites it
75 citing papers in PubMed, 3 syntheses or guidelines pooled it, 142 citations in OpenAlex.
- Japanese society for cancer of the colon and rectum (JSCCR) guidelines 2024 for the clinical practice of hereditary colorectal cancer.International journal of clinical oncology · 2026Guideline
- Guideline
- British Society of Gastroenterology position statement on serrated polyps in the colon and rectum.Gut · 2017Guideline
- Prevalence of intestinal spirochaetosis in serrated polyposis syndrome compared with other colorectal polyp conditions: a case-control study in Japan.BMJ open gastroenterology · 2026Article
- [Hereditary colorectal cancer].Pathologie (Heidelberg, Germany) · 2026Review
- Article
- A tti1 mutation in the Tel2-Tti1-Tti2 complex specifically eliminates the cellular function of Rad3ATR, but not that of other PIKKs in fission yeast.PLoS genetics · 2026Article
- Functional Characterization of Loss ofInternational journal of molecular sciences · 2026Article
- Rare genetic diseases associated with G-quadruplex-induced replication stress.Communications biology · 2026Review
- Familial colorectal cancer: search for novel predisposition genes.Human genomics · 2025Article
- Genetic predisposition to polyposis syndromes.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2025Review
- Oncogene-Induced Senescence Transcriptomes Signify Premalignant Colorectal Adenomas.Current issues in molecular biology · 2025Article
- Hereditary Colorectal Cancer: Clinical Implications of Genomic Medicine and Precision Oncology.Journal of the anus, rectum and colon · 2025Review
- Germline pathogenic variants in RNF43 in patients with and without serrated polyposis syndrome.Familial cancer · 2024Article
- Germline Variants in DNA Interstrand-Cross Link Repair Genes May Contribute to Increased Susceptibility for Serrated Polyposis Syndrome.International journal of molecular sciences · 2024Article
- The evolving roles of Wnt signaling in stem cell proliferation and differentiation, the development of human diseases, and therapeutic opportunities.Genes & diseases · 2024Review
- Inherited BRCA1 and RNF43 pathogenic variants in a familial colorectal cancer type X family.Familial cancer · 2024Article
- The Progress of Colorectal Polyposis Syndrome in Chinese Population.Clinics in colon and rectal surgery · 2023Review
- [Hereditary colorectal carcinogenesis].Pathologie (Heidelberg, Germany) · 2023Review
- Current status of molecular diagnostic approaches using liquid biopsy.Journal of gastroenterology · 2023Review
15 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 2 countries.
Funding
Abstract
BACKGROUND &
aimsLittle is known about the genetic factors that contribute to the development of sessile serrated adenomas (SSAs). SSAs contain somatic mutations in BRAF or KRAS early in development. However, evidence from humans and mouse models indicates that these mutations result in oncogene-induced senescence (OIS) of intestinal crypt cells. Progression to serrated neoplasia requires cells to escape OIS via inactivation of tumor suppressor pathways. We investigated whether subjects with multiple SSAs carry germline loss-of function mutations (nonsense and splice site) in genes that regulate OIS: the p16-Rb and ATM-ATR DNA damage response pathways.
methodsThrough a bioinformatic analysis of the literature, we identified a set of genes that function at the main nodes of the p16-Rb and ATM-ATR DNA damage response pathways. We performed whole-exome sequencing of 20 unrelated subjects with multiple SSAs; most had features of serrated polyposis. We compared sequences with those from 4300 subjects matched for ethnicity (controls). We also used an integrative genomics approach to identify additional genes involved in senescence mechanisms.
resultsWe identified mutations in genes that regulate senescence (ATM, PIF1, TELO2,XAF1, and RBL1) in 5 of 20 subjects with multiple SSAs (odds ratio, 3.0; 95% confidence interval, 0.9–8.9; P =.04). In 2 subjects,we found nonsense mutations in RNF43, indicating that it is also associated with multiple serrated polyps (odds ratio, 460; 95% confidence interval, 23.1–16,384; P = 6.8 x 10(-5)). In knockdown experiments with pancreatic duct cells exposed to UV light, RNF43 appeared to function as a regulator of ATMATRDNA damage response.
conclusionsWe associated germline loss-of-function variants in genes that regulate senescence pathways with the development of multiple SSAs.We identified RNF43 as a regulator of the DNA damage response and associated nonsense variants in this gene with a high risk of developing SSAs.
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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.