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Integrated genetic and epigenetic analysis of cancer-related genes in non-ampullary duodenal adenomas and intramucosal adenocarcinomas.

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 ?-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.

SUBMITTER: Ota R

PROVIDER: S-EPMC7693035 | biostudies-literature | 2020 Nov

REPOSITORIES: biostudies-literature

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Integrated genetic and epigenetic analysis of cancer-related genes in non-ampullary duodenal adenomas and intramucosal adenocarcinomas.

Ota Ryosuke R Sawada Takeshi T Tsuyama Sho S Sasaki Yasushi Y Suzuki Hiromu H Kaizaki Yasuharu Y Hasatani Kenkei K Yamamoto Eiichiro E Nakanishi Hiroyoshi H Inagaki Satoko S Tsuji Shigetsugu S Yoshida Naohiro N Doyama Hisashi H Minato Hiroshi H Nakamura Keishi K Kasashima Satomi S Kubota Eiji E Kataoka Hiromi H Tokino Takashi T Yao Takashi T Minamoto Toshinari T

The Journal of pathology 20200912 3

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 gl ...[more]

PMID: 32770675

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Project description:Background and aimsDuodenal polyps have a reported incidence of 0.3% to 4.6%. Sporadic, nonampullary duodenal adenomas (SNDAs) comprise less than 10% of all duodenal polyps, and ampullary adenomas are even less common. Nonetheless, the incidence continues to rise because of widespread endoscopy use. Duodenal polyps with villous features or those that are larger than 10 mm may raise concern for malignancy and require removal. We demonstrate endoscopic resection of SNDAs and ampullary adenomas using some of our preferred techniques.MethodsThe duodenum has several components that can make EMR of duodenal polyps technically challenging. Not only does the duodenum have a thin muscle layer, but it is also highly mobile and vascular, which may explain higher rates of perforation and bleeding of duodenal EMR reported in the literature compared with colon EMR. A standard adult gastroscope with a distal cap is commonly used for duodenal EMRs. Based on the location, however, side-viewing duodenoscopes or pediatric colonoscopes may be used. To prepare for EMR, a submucosal injection is performed for an adequate lift. The polyp is then resected via stiff monofilament snares and subsequently closed with hemostatic clips if feasible. The ampullectomy technique differs slightly from duodenal EMRs and carries the additional risk of pancreatitis. Submucosal injection in the ampulla may not lift well; thus, its utility is debatable. Biliary sphincterotomy should be performed, and based on endoscopist preference, the pancreatic duct (PD) guidewire can be left during resection to maintain access. After resection, a PD stent is placed to minimize pancreatitis risk.ResultsThe video shows the aforementioned duodenal EMR techniques. Two clips of ampullectomy are also shown in the video.ConclusionsA few common techniques used to perform duodenal EMR and ampullectomy are highlighted in the video. It is important to understand and manage adverse events associated with these procedures and to have established surveillance plans.

Project description:AbstractSporadic non-ampullary duodenal adenoma (SNADA) is a rare disease, and therefore, its clinical characteristics have not been comprehensively investigated. Furthermore, owing to the high complication rates and severity of endoscopic resection, treatment strategies vary among facilities. In the present study, we aimed to clarify the clinical characteristics and course of SNADA.We extracted clinical and histological records of SNADA cases diagnosed in 11 hospitals between September 1999 and August 2014. The patients were divided into "no-resection" and "resection" groups based on the initial treatment approach. We investigated the long-term outcome of the "no-resection" group and treatment results of the "resection" group, with particular interest in endoscopic resection.Overall, 299 patients were diagnosed with SNADA. The median age at diagnosis was 67 years (range, 31-88 years), with approximately twice as many men as women. The median tumor size was 8.0 mm (2-60 mm). In total, 161 patients were initially selected for no-resection and 138 underwent resection. Age >70 years and the presence of either severe illness or poor performance status were significantly related to opting for no-resection. In the no-resection group, 101 patients underwent endoscopic follow-up for at least 1 year. During the observational period (2.5 ± 2.2 years), 27 lesions (27%) disappeared following cold forceps biopsy, and 13 lesions (14%) presented lateral growth. Four lesions (4%) changed to mucosal carcinoma, 3 were treated endoscopically, and 1 was surgically resected. Nineteen patients died; however, no one died of duodenal carcinoma. In the endoscopic resection group, en bloc resection was achieved in 78% of patients. However, the complication rate for perforation was 7%, and endoscopic submucosal dissection was associated with a 36% perforation rate.With the low incidence of cancer development and no disease specific death, the strategy of initially not performing resection could be considered especially for the older adults, poor-prognosis patients, or small lesions.

Dataset Information

Integrated genetic and epigenetic analysis of cancer-related genes in non-ampullary duodenal adenomas and intramucosal adenocarcinomas.

Publications

Integrated genetic and epigenetic analysis of cancer-related genes in non-ampullary duodenal adenomas and intramucosal adenocarcinomas.

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