ArticleThe Journal of pathology2020
Integrated genetic and epigenetic analysis of cancer-related genes in non-ampullary duodenal adenomas and intramucosal adenocarcinomas.
Article in The Journal of pathology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed, 23 citations in OpenAlex.
- Tumours of the duodenum and the ampulla of Vater: An overview of the key criteria for their classification, pathogenesis, and molecular assessment.Virchows Archiv : an international journal of pathology · 2026Review
- Real-World Data of Comprehensive Genomic Profiles and Clinicopathological Characteristics of Duodenal Epithelial Neoplasms.Cancers · 2026Article
- Article
- Clinicopathological and Genetic Features in Superficial Nonampullary Duodenal Epithelial Tumors.Gastroenterology research and practice · 2025Article
- Synchronous Multiple Primary Malignant Adenocarcinoma of the Descending Colon and Fungating Bleeding Adenocarcinoma of the Terminal Ileum Presenting Massive Rectal Bleeding: A Trap for the Unwary.OncoTargets and therapy · 2024Article
- Identifying novel interactions of the colon-cancer related APC protein with Wnt-pathway nuclear transcription factors.Cancer cell international · 2022Article
- Genetic analysis of Japanese patients with small bowel adenocarcinoma using next-generation sequencing.BMC cancer · 2022Article
- The role of epigenetics in childhood autoimmune diseases with hematological manifestations.Pediatric investigation · 2022Review
- APC mutations are common in adenomas but infrequent in adenocarcinomas of the non-ampullary duodenum.Journal of gastroenterology · 2021Article
- Small Bowel Epithelial Precursor Lesions: A Focus on Molecular Alterations.International journal of molecular sciences · 2021Review
- Extensive molecular reclassification: new perspectives in small bowel adenocarcinoma?Medical oncology (Northwood, London, England) · 2021Article
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Authors and funding
21 authors at 6 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The molecular and clinical characteristics of non-ampullary duodenal adenomas and intramucosal adenocarcinomas are not fully understood because they are rare. To clarify these characteristics, we performed genetic and epigenetic analysis of cancer-related genes in these lesions. One hundred and seven non-ampullary duodenal adenomas and intramucosal adenocarcinomas, including 100 small intestinal-type tumors (90 adenomas and 10 intramucosal adenocarcinomas) and 7 gastric-type tumors (2 pyloric gland adenomas and 5 intramucosal adenocarcinomas), were investigated. Using bisulfite pyrosequencing, we assessed the methylation status of CpG island methylator phenotype (CIMP) markers and MLH1. Then using next-generation sequencing, we performed targeted exome sequence analysis within 75 cancer-related genes in 102 lesions. There were significant differences in the clinicopathological and molecular variables between small intestinal- and gastric-type tumors, which suggests the presence of at least two separate carcinogenic pathways in non-ampullary duodenal adenocarcinomas. The prevalence of CIMP-positive lesions was higher in intramucosal adenocarcinomas than in adenomas. Thus, concurrent hypermethylation of multiple CpG islands is likely associated with development of non-ampullary duodenal intramucosal adenocarcinomas. Mutation analysis showed that APC was the most frequently mutated gene in these lesions (56/102; 55%), followed by KRAS (13/102; 13%), LRP1B (10/102; 10%), GNAS (8/102; 8%), ERBB3 (7/102; 7%), and RNF43 (6/102; 6%). Additionally, the high prevalence of diffuse or focal nuclear β-catenin accumulation (87/102; 85%) as well as mutations of WNT pathway components (60/102; 59%) indicates the importance of WNT signaling to the initiation of duodenal adenomas. The higher than previously reported frequency of APC gene mutations in small bowel adenocarcinomas as well as the difference in the APC mutation distributions between small intestinal-type adenomas and intramucosal adenocarcinomas may indicate that the adenoma-carcinoma sequence has only limited involvement in duodenal carcinogenesis. © 2020 The Authors. The Journal of Pathology published by John Wiley & Sons, Ltd. on behalf of The Pathological Society of Great Britain and Ireland.
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