"colonic adenomatous polyposis of unknown etiology" OR "adenomatous polyposis of unknown aetiology" OR CPUE OR "Sporadic multiple adenomatous polyps"

… the adenomatous polyposis coli (APC) gene and is classically characterized by more than 100 colorectal adenomas, early onset of colorectal … pigment epithelium, polyposis of the upper …

… Colonic adenomatous polyposis of unknown etiology (CPUE) is diagnosed in patients with … predisposes to CRC or colonic polyps. We present a rare case of CPUE in a patient with …

… of multiple genetic and epigenetic alterations, which manifest the transition from normal colonic mucosa to adenocarcinomas via adenomas (or adenomatous polyps) … In sporadic CRCs, …

BACKGROUND AND AIMS For young individuals (age <40 years) without strong family histories that would put them at risk for genetic colorectal cancer syndromes, it is unclear if national Multi-Society Task Force surveillance recommendations apply or if endoscopists follow these guideline recommendations when such patients are incidentally found to have adenoma(s) on colonoscopy. METHODS We reviewed records on young (age <40 years) patients, with either no family history or only a moderate family history (1 first-degree family member with colorectal cancer at age ≥50), who were found to have neoplastic polyp(s) on their index colonoscopy. We assessed the pattern of endoscopist surveillance recommendations, whether endoscopist recommendations complied with national guidelines, and compliance with surveillance recommendations. RESULTS One hundred forty-one subjects were included, of whom 19 (13.5%) had a moderate family history of colorectal cancer. For patients with non-high-risk findings, 27.7% were asked to repeat their colonoscopy in ≤3 years and 99.0% within 5 years. Endoscopist surveillance recommendation compliance rates with national guidelines were >65.0% for low-risk neoplasia but lower for high-risk (40.0%), nonpolypoid (44.2%), and serrated neoplasia (54.2%, P < .001 for all). Subjects whose endoscopist recommendations were noncompliant with guidelines were usually recalled too early (96%). Only 24.7% of subjects were actually compliant with endoscopist surveillance recommendations. CONCLUSIONS For young patients with neoplastic polyp(s) but no strong family history, most endoscopists complied with national guidelines and recommended repeat colonoscopy in 3 to 5 years. However, relatively few patients were compliant with repeat colonoscopy recommendations. For most cases that were noncompliant with guidelines, patients were recalled too early as opposed to too late.

… characterized by the formation of multiple adenomatous polyps in the colon … colonic adenomatous polyposis of unknown etiology (CPUE) [12]. A relative lack of understanding of CPUE …

… Colonic adenomatous polyposis of unknown etiology (CPUE) … We present a rare case of CPUE in a patient with CDH1 … After a multi-disciplinary discussion, the decision was made …

ABSTRACT Despite extensive investigations into the microbiome and metabolome changes associated with colon polyps and colorectal cancer (CRC), the microbiome and metabolome profiles of individuals with colonic polyposis, including those with (Gene-pos) and without (Gene-neg) a known genetic driver, remain comparatively unexplored. Using colon biopsies, polyps, and stool from patients with Gene-pos adenomatous polyposis (N = 9), Gene-neg adenomatous polyposis (N = 18), and serrated polyposis syndrome (SPS, N = 11), we demonstrated through 16S rRNA sequencing that the mucosa-associated microbiota in individuals with colonic polyposis is representative of the microbiota associated with small polyps, and that both Gene-pos and SPS cohorts exhibit differential microbiota populations relative to Gene-neg polyposis cohorts. Furthermore, we used these differential microbiota taxa to perform linear discriminant analysis to differentiate Gene-neg subjects from Gene-pos and from SPS subjects with an accuracy of 89% and 93% respectively. Stool metabolites were quantified via 1H NMR, revealing an increase in alanine in SPS subjects relative to non-polyposis subjects, and Partial Least Squares Discriminant Analysis (PLS-DA) analysis indicated that the proportion of leucine to tyrosine in fecal samples may be predictive of SPS. Use of these microbial and metabolomic signatures may allow for better diagnostric and risk-stratification tools for colonic polyposis patients and their families as well as promote development of microbiome-targeted approaches for polyp prevention.

The development of genome-wide massively parallel sequencing, ie, whole-genome and whole-exome sequencing, and copy number approaches has raised high expectations for the identification of novel hereditary colorectal cancer genes. Although relatively successful for genes causing adenomatous polyposis syndromes, both autosomal dominant and recessive, the identification of genes associated with hereditary non-polyposis colorectal cancer has proven extremely challenging, mainly because of the absence of major high-penetrance genes and the difficulty in demonstrating the functional impact of the identified variants and their causal association with tumor development. Indeed, most, if not all, novel candidate non-polyposis colorectal cancer genes identified so far lack corroborative data in independent studies. Here we review the novel hereditary colorectal cancer genes and syndromes identified and the candidate genes proposed in recent years as well as discuss the challenges we face.

Background & Aims: Somatic mosaicism arises from genetic alterations that occur after the first division of the zygote, so that not in all cells in the body contain the same genetic variants. These variants might contribute to colorectal cancer (CRC) and polyposis syndromes. We performed a systematic review to provide a comprehensive overview of somatic mosaicism in patients with CRC and polyposis syndromes. Methods: We searched PubMed through March 2019 to identify reports of mosaicism in patients with CRC or polyposis syndromes. We divided the final set of studies into 3 subgroups describing APC mosaicism, mosaicism in other genes associated with susceptibility to CRC susceptibility, and epigenetic mosaicism. Results: Of the 232 articles identified in our systematic search, 46 met the criteria for further analysis. Of these, 35 studies described mosaic variants or epimutations in patients with CRC or polyposis syndromes. Nineteen studies described APC mosaicism, comprising a total of 57 patients. Six described mosaicism in genes associated with familial CRC syndromes, such as Lynch and Cowden syndromes. Ten studies described epigenetic mosaicism, sometimes resulting from a germline variant (such as deletion of EPCAM). Conclusions: In a systematic review, we found that many patients with polyposis syndromes have genetic mosaicism, most frequently in APC variants; this information can be used in management of patients. Mosaicism in genes associated with susceptibility to CRC contributes to development of other familial CRC syndromes. Heritable epigenetic mosaicism is likely underestimated and could have a dominant pattern of inheritance. However, the inheritance of primary mosaic epimutations, without an genetic cause, is complex and not fully understood.

… A substantial proportion of patients with adenomatous polyposis have de novo … polyposis. Diagnosing mosaicism allows patients to be managed using familial adenomatous polyposis (…

The risk of periampullary cancer in patients with classic familial adenomatous polyposis (FAP) is significantly increased compared with the general population. However, the incidence of this extracolonic manifestation in attenuated FAP (AFAP) is unknown. We report the case of a 38 year old woman with no known family history of polyposis or colorectal cancer, who presented with ampullary adenocarcinoma. Diagnosis of AFAP was made only after evaluation of the patient’s extended family history and genetic testing. This case report suggests that AFAP should be included in the differential diagnosis of patients with ampullary/duodenal tumours.

Background: Patients with multiple colorectal adenomas (MCRA) without genetic cause are increasingly being diagnosed. The characteristics and natural history of this condition are not well studied. Materials and Methods: Twenty-seven patients with MCRA, with cumulatively 10 to 99 colorectal adenomas and without deleterious mutations of APC or MYH genes, were investigated. Results of colonoscopies with a mean follow-up of 4.9 years (range, 0 to 27 y) were evaluated. Findings from esophagogastroduodenoscopy and extracolonic manifestations were assessed. Results: The mean age at polyp diagnosis and MCRA diagnosis was 47.8±13.1 years (range, 21 to 72 y) and 50.4±14.6 years (range, 21 to 72 y), respectively. In 22% of patients another family member had MCRA. At first colonoscopy, the mean number of adenomas was 35.0±35.9 (range, 0 to 99). Serrated polyps were rare. Esophagogastroduodenoscopy revealed 47% of patients had upper tract neoplasia. Patients with upper tract findings were diagnosed with MCRA at significantly younger mean age than those without findings, P<0.05. Eighteen patients (67%) underwent colectomy with a mean time from diagnosis of MCRA of 3.1±1.3 years. After surgery, surveyed patients developed recurrent adenomas in retained colorectum. Nine patients (33%) had extracolonic cancers. Conclusions: MCRA patients have a similar clinicopathologic phenotype to known syndromes of attenuated adenomatous polyposis and the majority have need for colectomy. The management of MCRA patients and families should parallel that of attenuated familial adenomatous polyposis and MUTYH-associated polyposis including surveillance of the upper tract.

… heterogeneous, given that no germ-line APC mutation can be found in some patients despite … with multiple colorectal adenomas and a group of patients with classic adenomatous …

Background: Development of more than 100 colorectal adenomas is diagnostic of the dominantly inherited autosomal disease familial adenomatous polyposis (FAP). Germline mutations can be identified in the adenomatous polyposis coli ( APC ) gene in approximately 80% of patients. The APC protein comprises several regions and domains for interaction with other proteins, and specific clinical manifestations are associated with the mutation assignment to one of these regions or domains. Aims: The phenotype in patients without an identified causative APC mutation was compared with the phenotype in patients with a known APC mutation and with the phenotypes characteristic of patients with mutations in specific APC regions and domains. Patients: Data on 121 FAP probands and 149 call up patients from 70 different families were extracted from the Danish Polyposis register. Methods: Differences in 16 clinical manifestations were analysed according to the patient’s mutational status. Two sided independent t sample test, two sided χ 2 test, and odds ratios were calculated. Results: Patients without identified APC mutations had a unique and severe phenotype, which was roughly described as: young age at diagnosis and subsequent death in spite of development of few colorectal adenomas; low risk of involvement of the upper gastrointestinal tract, as reflected by a low mean Spigelman stage, and a low risk of fundic gland polyposis. Finally, they had significantly fewer affected family members, although they do not themselves more often represent an isolated case. Conclusions: The severe phenotype should be considered when counselling FAP families in which attenuated FAP is excluded and in which a causative APC mutation has not been identified.

… those with ≥ 20 adenomas in their oligopolyposis cohort. Pathogenic mutations were found … of oligopolyposis patients in this study in comparison with other oligopolyposis studies is …

… Colorectal cancer is the second leading cause of cancer death, after lung cancer, in the USA… The characteristics of the attenuated variant include oligopolyposis (fewer than 100 …

The current understanding of familial colorectal cancer was limited to descriptions of affected pedigrees until the early 1990s. A series of landscape‐altering discoveries revealed that there were distinct forms of familial cancer, and most were related to genes previously not known to be involved in human disease. This review largely focuses on advances in our understanding of Lynch syndrome because of the unique relationship of this disease to defective DNA mismatch repair and the clinical implications this has for diagnostics, prevention, and therapy. Recent advances have occurred in our understanding of the epidemiology of this disease, and the advent of broad genetic panels has altered the approach to germline and somatic diagnoses for all of the familial colorectal cancer syndromes. Important advances have been made toward a more complete mechanistic understanding of the pathogenesis of neoplasia in the setting of Lynch syndrome, and these advances have important implications for prevention. Finally, paradigm‐shifting approaches to treatment of Lynch‐syndrome and related tumors have occurred through the development of immune checkpoint therapies for hypermutated cancers. CA Cancer J Clin 2018;68:217–231. © 2018 American Cancer Society.