Cyclooxygenase‐2 Expression in Polyps From a Patient With Juvenile Polyposis Syndrome With Mutant <i>BMPR1A</i>

Kurland, Jayde; Beck, Stayce E.; Solomon, Carol; Brann, Oscar S.; Carethers, John M.; Huang, Shiang

doi:10.1097/mpg.0b013e31802e98e5

Cited by 15 publications

(14 citation statements)

References 32 publications

(40 reference statements)

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“…Interestingly, although not significant, BMPR1A germline mutation carriers showed an increase in COX-2 expression compared with JPS patients without a detected germline mutation. These findings are in line with Kurland et al,32 who recently described high COX-2 expression in one patient carrying a BMPR1A mutation. JPS patients with a SMAD4 germline mutation on the other hand did not have increased COX-2 expression, even though SMAD4 germline mutation carriers have been described as possessing a more aggressive intestinal phenotype 15.…”

Section: Discussionsupporting

confidence: 92%

Increased Cyclooxygenase-2 Expression in Juvenile Polyposis Syndrome

Hattem

Brosens

Marks

et al. 2009

Clinical Gastroenterology and Hepatology

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Background & Aims-Gastrointestinal juvenile polyps may occur in juvenile polyposis syndrome (JPS) or sporadically. JPS is an autosomal-dominant condition caused by a germline defect in SMAD4 or BMPR1A in 50% to 60% of cases, and is characterized by multiple juvenile polyps, predominantly in the colorectum. JPS has an increased risk of gastrointestinal malignancy but sporadic juvenile polyps do not. Cyclooxygenase-2 (COX-2) expression is increased in gastrointestinal tumorigenesis and familial adenomatous polyposis. Inhibition of COX-2 leads to regression of colorectal adenomas in familial adenomatous polyposis patients and inhibits gastrointestinal tumorigenesis. To investigate the role of COX-2 in juvenile polyps, we compared the expression of COX-2 in juvenile polyps from a well-defined group of juvenile polyposis patients and sporadic juvenile polyps.

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Section: Discussionsupporting

confidence: 92%

Increased Cyclooxygenase-2 Expression in Juvenile Polyposis Syndrome

Hattem

Brosens

Marks

et al. 2009

Clinical Gastroenterology and Hepatology

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“…This mutation causes abnormal splicing between exons 3 and 4 and potentially alters PTEN phosphatase function 23. One patient diagnosed with JPS was found to carry a germline mutation in BMPR1A 28. DNA from 3 of the 4 remaining patients was sequenced for mutations in PTEN and SMAD4 and the dominant mutations in BMRP1A (1 patient was not available for DNA analysis).…”

Section: Resultsmentioning

confidence: 99%

“…23 One patient diagnosed with JPS was found to carry a germline mutation in BMPR1A. 28 We performed microdissection followed by microsatellite analysis on domains from familial hamartomatous polyps in an attempt to characterize the genetic pattern that could drive neoplastic pathogenesis or transformation. The numbers of domains (consisting of surface epithelium, cystic epithelium, and lamina propria) as well as the number of polyps examined are listed in Table 1.…”

Section: Germline Mutations Of Patients With Hamartomatous Polyposis mentioning

confidence: 99%

Evidence for an hMSH3 defect in familial hamartomatous polyps

Huang

Lee

Smith

et al. 2010

Cancer

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BACKGROUND:Patients with hamartomatous polyposis syndromes have increased risk for colorectal cancer (CRC). Although progression of polyps to carcinoma is observed, pathogenic mechanisms remain unknown. The authors examined whether familial hamartomatous polyps harbor defects in DNA mismatch repair (MMR), and assayed for somatic mutation of PTEN, a gene inactivated in the germline of some hamartomatous polyposis syndrome patients. METHODS: Ten hamartomatous polyposis syndrome patients were genotyped for germline mutations. Epithelial and nonepithelial polyp DNA were assayed for microsatellite instability (MSI) and PTEN frameshift mutation. DNA MMR and PTEN protein expression were assessed in all polyps by immunohistochemistry. In addition, 99 MSI-high sporadic CRCs and 50 each of hMLH1 À/À and hMSH3 À/À cell clones were examined for PTEN frameshifts. RESULTS: Twenty-five (58%) of 43 hamartomatous polyposis syndrome polyps demonstrated dinucleotide or greater MSI in polyp epithelium, consistent with hMSH3 deficiency. MSI domains lost hMSH3 expression, and PTEN expression was lost in polyps from germline PTEN patients; sporadic hamartomatous polyps did not show any of these findings. PTEN analysis revealed wild type exon 7 and 8 sequences suggestive of nonexistent or rare events for PTEN frameshifts; however, MSI-high sporadic CRC showed 11 (11%) of 99 frameshifts within PTEN, with 4 tumors having complete loss of PTEN expression. Subcloning hMLH1 À/À and hMSH3 À/À cells revealed somatic PTEN frameshifts in 4% and 12% of clones, respectively. CONCLUSIONS: Nondysplastic epithelium from hamartomatous polyposis syndrome polyps harbors hMSH3 defects, which may prime neoplastic transformation. Polyps from PTEN þ/À patients lose PTEN expression, but loss is not a universal early feature of all hamartomatous polyposis syndrome. However, PTEN frameshifts can occur in hMSH3-deficient cells, suggesting that hMSH3 deficiency could drive hamartomatous polyposis syndrome tumorigenesis. Cancer 2011;117:492

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“…Cyclooxygenase-2 (COX-2) expression may be increased in JPS 66 67. There exists a theoretical potential benefit in the use of selective COX-2 inhibitors in JPS or PJS,66–68 but to date there are no trials demonstrating efficacy.…”

Section: Prevention and Lifestyle Modification In Familial Crcmentioning

confidence: 99%

Guidelines for the management of hereditary colorectal cancer from the British Society of Gastroenterology (BSG)/Association of Coloproctology of Great Britain and Ireland (ACPGBI)/United Kingdom Cancer Genetics Group (UKCGG)

Monahan

Bradshaw²,

Dolwani

et al. 2019

Gut

312

375

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Heritable factors account for approximately 35% of colorectal cancer (CRC) risk, and almost 30% of the population in the UK have a family history of CRC. The quantification of an individual’s lifetime risk of gastrointestinal cancer may incorporate clinical and molecular data, and depends on accurate phenotypic assessment and genetic diagnosis. In turn this may facilitate targeted risk-reducing interventions, including endoscopic surveillance, preventative surgery and chemoprophylaxis, which provide opportunities for cancer prevention. This guideline is an update from the 2010 British Society of Gastroenterology/Association of Coloproctology of Great Britain and Ireland (BSG/ACPGBI) guidelines for colorectal screening and surveillance in moderate and high-risk groups; however, this guideline is concerned specifically with people who have increased lifetime risk of CRC due to hereditary factors, including those with Lynch syndrome, polyposis or a family history of CRC. On this occasion we invited the UK Cancer Genetics Group (UKCGG), a subgroup within the British Society of Genetic Medicine (BSGM), as a partner to BSG and ACPGBI in the multidisciplinary guideline development process. We also invited external review through the Delphi process by members of the public as well as the steering committees of the European Hereditary Tumour Group (EHTG) and the European Society of Gastrointestinal Endoscopy (ESGE). A systematic review of 10 189 publications was undertaken to develop 67 evidence and expert opinion-based recommendations for the management of hereditary CRC risk. Ten research recommendations are also prioritised to inform clinical management of people at hereditary CRC risk.

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Cyclooxygenase‐2 Expression in Polyps From a Patient With Juvenile Polyposis Syndrome With Mutant BMPR1A

Cited by 15 publications

References 32 publications

Increased Cyclooxygenase-2 Expression in Juvenile Polyposis Syndrome

Increased Cyclooxygenase-2 Expression in Juvenile Polyposis Syndrome

Evidence for an hMSH3 defect in familial hamartomatous polyps

Guidelines for the management of hereditary colorectal cancer from the British Society of Gastroenterology (BSG)/Association of Coloproctology of Great Britain and Ireland (ACPGBI)/United Kingdom Cancer Genetics Group (UKCGG)

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