Gastric tumours in FAP

Walton, Stephen J.; Frayling, Ian Martin; Clark, Susan; Latchford, Andrew

doi:10.1007/s10689-017-9966-0

Cited by 50 publications

(65 citation statements)

References 28 publications

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“…Moreover, a recent work shows that even in advanced cancers, where other oncogenic mutations are detected, APC loss is crucial for tumor maintenance and its restoration may lead to tumor regression. 26 This is also consistent with other studies done in mouse models 27 and the human CRC cell line SW40, 28 demonstrating that restoring full-length APC alone attenuates tumor growth, despite other oncogenic mutations.…”

Section: Discussionsupporting

confidence: 90%

Resorting the function of the colorectal cancer gatekeeper adenomatous polyposis coli

Kariv

Caspi

Fliss-Isakov³

et al. 2019

Intl Journal of Cancer

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As a large number of cancers are caused by nonsense mutations in key genes, read‐through of these mutations to restore full‐length protein expression is a potential therapeutic strategy. Mutations in the adenomatous polyposis coli (APC) gene initiate the majority of both sporadic and hereditary colorectal cancers (CRC) and around 30% of these mutations are nonsense mutations. Our goal was to test the feasibility and effectiveness of APC nonsense mutation read‐through as a potential chemo‐preventive therapy in Familial Adenomatous Polyposis (FAP), an inherited CRC syndrome patients. Ten FAP patients harboring APC nonsense mutations were treated with the read‐through inducing antibiotic erythromycin for 4 months. Endoscopic assessment of the adenomas was performed at baseline, after 4 and after 12 months. Adenoma burden was documented in terms of adenoma number, maximal polyp size and cumulative polyp size per procedure. Tissue samples were collected and subjected to molecular and genetic analyses. Our results show that in the majority of patients the treatment led to a decrease in cumulative adenoma burden, median reduction in cumulative adenoma size and median reduction in adenoma number. Molecular and genetic analyses of the adenomas revealed that the treatment led to a reduced number of somatic APC mutations, reduced cellular proliferation and restoration of APC tumor‐suppressing activity. Together, our findings show that induced read‐through of APC nonsense mutations leads to promising clinical results and should be further investigated to establish its therapeutic potential in FAP and sporadic CRCs harboring nonsense APC mutations.

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Section: Discussionsupporting

confidence: 90%

Resorting the function of the colorectal cancer gatekeeper adenomatous polyposis coli

Kariv

Caspi

Fliss-Isakov³

et al. 2019

Intl Journal of Cancer

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“…Consistent with previous reports, in the present study, GN showed whitish coalescent nodules in the proximal stomach. 7,17 For early detection of GN in the AG-negative group, the above-mentioned characteristic findings are very useful.…”

Section: Discussionmentioning

confidence: 99%

“…In studies from Western countries, most cases were associated with FGP, and nearly half of these cases were of advanced cancer and showed a poor prognosis. 7,8,17 Regarding the association between gastric phenotype and GN with FGP, GN with advanced cancer seemed to have the gastric phenotype. In sporadic cases, the gastric phenotype had a high potential for malignancy.…”

Section: Discussionmentioning

confidence: 99%

“…5,6 However, in recent years in Western countries, there have been reports of gastric carcinoma (GCA) associated with FGP, including advanced cancer. 7,8 Moreover, gastric adenoma (GAD), which roughly corresponds to low-grade dysplasia, is less frequently encountered compared to FGP and is mainly found in the distal stomach. 9 Frequency of GCA in FAP patients was reported to be 2.6-13.6% in Japan 10-12 and 2.7-4.2% in Korea.…”

Section: Introductionmentioning

confidence: 99%

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Phenotypic variations of gastric neoplasms in familial adenomatous polyposis are associated with endoscopic status of atrophic gastritis

Nakano¹,

Kawachi²,

Chino

et al. 2019

Digestive Endoscopy

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Background and Aim: Gastric neoplasms (GN), including gastric adenoma and carcinoma, are well known as extracolonic manifestations of familial adenomatous polyposis (FAP). We aimed to investigate the clinicopathological features of GN in FAP patients and to clarify their relationship with the endoscopic status of the background mucosa. Methods:We analyzed the records of 39 patients who were diagnosed with FAP and underwent esophagogastroduodenoscopy between April 2005 and July 2016. Patients were divided into two groups according to atrophic gastritis (AG) status. Endoscopic findings of GN and background mucosa, and histopathological findings, including phenotypic expression of GN and mutation locus of adenomatous polyposis coli (APC) gene, were evaluated.Results: Gastric neoplasms were more predominant in the AG-positive group than in the AG-negative group (6/9, 66.7% vs 7/30, 23.3%; P = 0.039). Of 36 GN detected in 13 patients, six GN in five patients were followed and 30 GN in eight patients were endoscopically resected and analyzed. GN in the AGnegative group frequently showed whitish color, were located in the proximal stomach, and presented the gastric immunophenotype compared to GN in the AG-positive group. All GN were intramucosal lesions and were curatively resected regardless of AG status. APC germline mutations were identified in 32 patients. In patients with GN, a significantly higher number of mutation loci were among exons 10-15 (codons 564-1465).Conclusion: Clinicopathological characteristics and phenotypic expressions of GN in FAP patients depend on background mucosa status with or without AG. These findings are useful for detecting GN in FAP patients.

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“…Upper gastrointestinal (UGI) tract surveillance has been recommended, starting from 25 years of age and has been shown to be beneficial. 3 Although the data are less, gastric adenomas and cancer are being noticed as newly emerging clinical problems [4][5][6] ; this may be partly due to increased endoscopic detection. More than 90% of patients will develop duodenal adenomas during their lifetime.…”

Section: Colorectalmentioning

confidence: 99%

Practical management of polyposis syndromes

Patel

Hyer

2019

Frontline Gastroenterol

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Hereditary bowel tumours are usually part of a distinct syndrome which require management of both intestinal and extra-intestinal disease. Polyposis syndromes include: Familial adenomatous polyposis, MUTYH-associated polyposis, Serrated polyposis syndrome, Peutz-Jeghers syndrome, Juvenile polyposis syndrome and PTEN-hamartomatous syndromes. Of all colorectal cancers (CRC), 5%–10% will be due to an underlying hereditary CRC syndrome. Diagnosis and management of polyposis syndromes is constantly evolving as new scientific and technological advancements are made with respect to identifying causative genes and increased sophistication of endoscopic therapy to treat polyps. This, in addition to data yielded from meticulous record-keeping by polyposis registries has helped to guide management in what are otherwise relatively rare conditions. These data help guide clinical management of patients and their ‘at-risk’ relatives. Diagnosis is both genetic where possible but clinical recognition is key in the absence of an identifiable causative gene. Furthermore, some syndromes can overlap which can additionally complicate diagnosis. The principle goals of polyposis management are first to manage and treat the presenting patient and then to identify ‘at-risk’ patients, through screening and predictive genetic testing, endoscopic surveillance to allow therapy and guide surgical prophylaxis. Due to the complexity of diagnosis and management, patients and their families should be referred to a genetics centre or a polyposis registry where dedicated management can take place.

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Gastric tumours in FAP

Cited by 50 publications

References 28 publications

Resorting the function of the colorectal cancer gatekeeper adenomatous polyposis coli

Resorting the function of the colorectal cancer gatekeeper adenomatous polyposis coli

Phenotypic variations of gastric neoplasms in familial adenomatous polyposis are associated with endoscopic status of atrophic gastritis

Practical management of polyposis syndromes

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