Frequency and Features of Duodenal Adenomas in Patients With MUTYH-Associated Polyposis

Walton, Stephen J.; Kallenberg, Frank G.J.; Clark, Susan; Dekker, Evelien; Latchford, Andrew

doi:10.1016/j.cgh.2016.02.020

Cited by 41 publications

(47 citation statements)

References 19 publications

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“…In a multicenter retrospective study of MAP, duodenal polyps were noted in 26 of 150 (17%) patients undergoing duodenoscopy and the lifetime risk of duodenal cancer was estimated at 4% (3). A more recent study in two specialist centers identified duodenal adenomas in 31 of 92 (34%) MAP patients undergoing endoscopy at a median age of 50 years (4).…”

Section: Introductionmentioning

confidence: 99%

Burden and Profile of Somatic Mutation in Duodenal Adenomas from Patients with Familial Adenomatous- and MUTYH-associated Polyposis

Thomas

Hurley

Meuser

et al. 2017

Clinical Cancer Research

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Purpose: Duodenal polyposis and cancer are important causes of morbidity and mortality in familial adenomatous polyposis (FAP) and MUTYH-associated polyposis (MAP). This study aimed to comprehensively characterize somatic genetic changes in FAP and MAP duodenal adenomas to better understand duodenal tumorigenesis in these disorders.Experimental Design: Sixty-nine adenomas were biopsied during endoscopy in 16 FAP and 10 MAP patients with duodenal polyposis. Ten FAP and 10 MAP adenomas and matched blood DNA samples were exome sequenced, 42 further adenomas underwent targeted sequencing, and 47 were studied by array comparative genomic hybridization. Findings in FAP and MAP duodenal adenomas were compared with each other and to the reported mutational landscape in FAP and MAP colorectal adenomas.Results: MAP duodenal adenomas had significantly more protein-changing somatic mutations (P ¼ 0.018), truncating mutations (P ¼ 0.006), and copy number variants (P ¼ 0.005) than FAP duodenal adenomas, even though MAP patients had lower Spigelman stage duodenal polyposis. Fifteen genes were significantly recurrently mutated. Targeted sequencing of APC, KRAS, PTCHD2, and PLCL1 identified further mutations in each of these genes in additional duodenal adenomas. In contrast to MAP and FAP colorectal adenomas, neither exome nor targeted sequencing identified WTX mutations (P ¼ 0.0017).Conclusions: The mutational landscapes in FAP and MAP duodenal adenomas overlapped with, but had significant differences to those reported in colorectal adenomas. The significantly higher burden of somatic mutations in MAP than FAP duodenal adenomas despite lower Spigelman stage disease could increase cancer risk in the context of apparently less severe benign disease.

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Section: Introductionmentioning

confidence: 99%

Burden and Profile of Somatic Mutation in Duodenal Adenomas from Patients with Familial Adenomatous- and MUTYH-associated Polyposis

Thomas

Hurley

Meuser

et al. 2017

Clinical Cancer Research

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“…The reported data on risk progression to cancer in MAP patients is less inclusive. Recently, Walton et al [16] conducted a study on MAP patients with duodenal polyposis found in 34% of cases. Analogous to FAP, the increasing size of DA and villous change led to the progression to carcinoma.…”

Section: Discussion/conclusionmentioning

confidence: 99%

“…Furthermore, patients with determined MAP have an estimated lifetime duodenal cancer risk of up to 4%. Analogous to FAP, factors promoting adenoma progression in MAP are increasing adenoma size and villous histological type [12,16].…”

Section: Introductionmentioning

confidence: 99%

Assessment of Duodenal Adenomas and Strategies for Curative Therapy

Pavlovic-Markovic

Dragašević²,

Krstić

et al. 2019

Dig Dis

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Background: The increasing incidence of duodenal neoplasm has underlined different methods of resection depending on the clinical presentation, endoscopic features and histopathology. In this comprehensive review, we systematically describe the current knowledge concerning the diagnosis and management of duodenal adenomas (DAs) and discuss data considering all possible therapeutic approaches. Summary: Among a variety of duodenal lesions, including neuroendocrine tumors and gastrointestinal stromal tumors, DAs present precancerous lesions of the duodenal papilla or non-ampullary region necessitating removal. DAs can occur sporadically (SDA) as rare lesions or relatively common in polyposis syndromes. The endoscopic resections of DA are associated with an increased degree of complexity due to distinctive anatomical properties of the duodenal wall, luminal diameter and the presence of ampulla with pancreatic and biliary drainage. The endoscopic techniques including cold snare polypectomy (CSP), endoscopic mucosal resection (EMR), and argon plasma coagulation ablation are suggested to be less invasive than surgical treatment, associated with shorter hospital stay and lower cost. According to the current clinical practice, surgery has been accepted as standard therapeutic approach in familial adenomatous polyposis patients with severe polyposis or DA not amenable to endoscopic resection. Key Messages: The strategy for endoscopic resection of DAs depends on the lesion size, morphology, location, and histopathology findings. Small adenomas are most frequently diagnosed and removed by standard CSP techniques, while large laterally spreading lesions and ampullary adenoma are referred for EMR or endoscopic papillectomy respectively. Screening colonoscopy is indicated in patients with SDA. Additional studies for new endoscopic strategies and techniques for curative therapy of DAs are needed to refine future management decisions. Complete resection of DA is considered curative, but nevertheless, long-term endoscopic follow-up is still required to detect and treat any recurrent arising lesions.

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“…Duodenal neoplasia is also a risk in this condition, with polyps developing in 4% to 25% of individuals and a variety of other rare extraintestinal features also being described. 14,15,72,73 Because of the overlapping phenotype of AFAP and MAP, genetic testing, usually with a parallel or reflexive approach, should include molecular testing for both the APC and MUTYH genes. 25 Similar to FAP, testing for MUTYH should be considered per NCCN guidelines when one of the following conditions is met: (1) more than 20 adenomas in the colon or rectum over the lifetime of the patient, (2) known diagnosis of MAP in the Tumors from individuals should be tested for MSI in the following situations: a) CRC diagnosed in a patient who is younger than 50 years b) Presence of synchronous, or metachronous, colorectal or other Lynch syndromeerelated tumors regardless of patient age c) CRC with MSI-high histology diagnosed in a patient who is younger than 60 years d) CRC diagnosed in a patient with one or more first-degree relatives with a Lynch syndromeerelated cancer, with one of the cancers diagnosed before age 50 years e) CRC diagnosed in a patient with 2 or more firstor second-degree relatives with Lynch syndromeerelated cancer regardless of patient age a CRC ¼ colorectal cancer; MSI ¼ microsatellite instability.…”

Section: Mutyh-associated Polyposismentioning

confidence: 99%

Hereditary Cancer Syndromes—A Primer on Diagnosis and Management, Part 2: Gastrointestinal Cancer Syndromes

Samadder

Baffy

Giridhar

et al. 2019

Mayo Clinic Proceedings

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Hereditary causes due to mutations and defects in certain genes account for roughly 5% to 10% of all colorectal cancers. These inherited syndromes have been associated with a 60% to 100% lifetime risk for development of colorectal cancer, depending on the genetic syndrome, and many also carry an increased risk for multiple extracolonic malignancies. In this second part of a review series on hereditary cancer syndromes, the focus will be to provide guidance on the features and management of the most commonly encountered hereditary colorectal cancers and polyposis conditions including Lynch syndrome, familial adenomatous polyposis, MUTYH-associated polyposis, and hamartomatous polyposis.

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Frequency and Features of Duodenal Adenomas in Patients With MUTYH-Associated Polyposis

Cited by 41 publications

References 19 publications

Burden and Profile of Somatic Mutation in Duodenal Adenomas from Patients with Familial Adenomatous- and MUTYH-associated Polyposis

Burden and Profile of Somatic Mutation in Duodenal Adenomas from Patients with Familial Adenomatous- and MUTYH-associated Polyposis

Assessment of Duodenal Adenomas and Strategies for Curative Therapy

Hereditary Cancer Syndromes—A Primer on Diagnosis and Management, Part 2: Gastrointestinal Cancer Syndromes

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