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Current Opinion in Pediatrics Oct 2021Polyposis syndromes are rare but significant entities that often present during childhood and adolescence. Polyposis syndromes should remain high on the differential... (Review)
Review
PURPOSE OF REVIEW
Polyposis syndromes are rare but significant entities that often present during childhood and adolescence. Polyposis syndromes should remain high on the differential diagnoses for any child presenting with rectal bleeding, protein-losing enteropathy or intussusception in the setting of multiple polyps in the gastrointestinal tract. There are three primary paediatric polyposis syndromes: Juvenile polyposis syndrome (JPS), Familial adenomatous polyposis (FAP) and Peutz-Jeghers syndrome (PJS). This review will cover recent guidelines for these conditions and advances in genetic testing.
RECENT FINDINGS
The first set of paediatric guidelines were released in 2019 by the European Society for Pediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN) for FAP, JPS and PJS. Even with advances in genetic testing, a significant proportion of patients with polyposis syndromes have no identifiable genetic mutations. Recent research has shown that polyps behave differently in patients with and without disease-causing variants, emphasizing the role of genetic testing in the diagnosis and management of polyposis syndromes.
SUMMARY
Polyposis syndromes in the paediatric population are growing due to increased recognition and advances in genetic testing. A timely diagnosis and surveillance of a paediatric polyposis syndrome are pivotal for the management of disease burden and early identification of cancers within the gastrointestinal tract and beyond. Paediatricians, paediatric gastroenterologists, paediatric oncologists and paediatric surgeons should be familiar with the presentation and comorbidities of polyposis syndromes in children and adolescents. Further research into genotype-phenotype correlations is needed to tailor the care for paediatric patients with polyposis syndromes.
Topics: Adenomatous Polyposis Coli; Adolescent; Child; Colorectal Neoplasms; Cost of Illness; Humans; Neoplastic Syndromes, Hereditary; Peutz-Jeghers Syndrome
PubMed: 34261898
DOI: 10.1097/MOP.0000000000001044 -
Annals of Coloproctology Dec 2021The genomic causes and clinical manifestations of hereditary colorectal cancer (HCRC) might be stratified into 2 groups, namely, familial (FCRC) and a limited sense of... (Review)
Review
The genomic causes and clinical manifestations of hereditary colorectal cancer (HCRC) might be stratified into 2 groups, namely, familial (FCRC) and a limited sense of HCRC, respectively. Otherwise, FCRC is canonically classified into 2 major categories; Lynch syndrome (LS) or associated spectra and inherited polyposis syndrome. By contrast, despite an increasing body of genotypic and phenotypic traits, some FCRC cannot be clearly differentiated as definitively single type, and the situation has become more complex as additional causative genes have been discovered. This review provides an overview of HCRC, including 6 LS or associated spectra and 8 inherited polyposis syndromes, according to molecular pathogenesis. Variants and newly-identified FCRC are particularly emphasized, including MUTYH (or MYH)-associated polyposis, Muir-Torre syndrome, constitutional mismatch repair deficiency, EPCAM-associated LS, polymerase proofreading-associated polyposis, RNF43- or NTHL1-associated serrated polyposis syndrome, PTEN hamartoma tumor syndrome, and hereditary mixed polyposis syndrome. We also comment on the clinical utility of multigene panel tests, focusing on comprehensive cancer panels that include HCRC. Finally, HCRC surveillance strategies are recommended, based on revised or notable concepts underpinned by competent validation and clinical implications, and favoring major guidelines. As hereditary syndromes are mainly attributable to genomic constitutions of distinctive ancestral groups, an integrative national HCRC registry and guideline is an urgent priority.
PubMed: 34961301
DOI: 10.3393/ac.2021.00878.0125 -
Clinical Case Reports Jan 2020Juvenile polyposis syndrome (JPS) patients can have a significantly high burden of polyposis. Patient who undergoes prophylactic colectomy for polyps not amenable to...
Juvenile polyposis syndrome (JPS) patients can have a significantly high burden of polyposis. Patient who undergoes prophylactic colectomy for polyps not amenable to endoscopic treatments requires close clinical surveillance to negate risk of malignancy from interval polyposis.
PubMed: 31998494
DOI: 10.1002/ccr3.2616 -
Gastrointestinal Endoscopy Nov 2017
Topics: Adult; Colonoscopy; Humans; Intestinal Polyposis; Male; Nail Diseases; Tongue Diseases
PubMed: 28576394
DOI: 10.1016/j.gie.2017.05.028 -
European Journal of Cell Biology 2022Adenomatous Polyposis Coli (APC) protein is mostly known as a tumor suppressor that regulates Wnt signaling, but is also an important cytoskeletal protein. Mutations in... (Review)
Review
Adenomatous Polyposis Coli (APC) protein is mostly known as a tumor suppressor that regulates Wnt signaling, but is also an important cytoskeletal protein. Mutations in the APC gene are linked to colorectal cancer and various neurological disorders and intellectual disabilities. Cytoskeletal functions of APC appear to have significant contributions to both types of these disorders. As a cytoskeletal protein, APC can regulate both actin and microtubule cytoskeletons, which together form the main machinery for cell migration. As APC is a multifunctional protein with numerous interaction partners, the complete picture of how APC regulates cell motility is still unavailable. However, some molecular mechanisms begin to emerge. Here, we review available information about roles of APC in cell migration and propose a model explaining how microtubules, using APC as an intermediate, can initiate leading edge protrusion in response to external signals by stimulating Arp2/3 complex-dependent nucleation of branched actin filament networks via a series of intermediate events.
Topics: Actins; Adenomatous Polyposis Coli Protein; Cell Movement; Genes, APC; Humans; Microtubules
PubMed: 35483122
DOI: 10.1016/j.ejcb.2022.151228 -
Digestive Diseases and Sciences Jul 2023The most prevalent type of intestinal polyposis, colorectal adenomatous polyposis (CAP), is regarded as a precancerous lesion of colorectal cancer with obvious genetic... (Review)
Review
The most prevalent type of intestinal polyposis, colorectal adenomatous polyposis (CAP), is regarded as a precancerous lesion of colorectal cancer with obvious genetic characteristics. Early screening and intervention can significantly improve patients' survival and prognosis. The adenomatous polyposis coli (APC) mutation is believed to be the primary cause of CAP. There is, however, a subset of CAP with undetectable pathogenic mutations in APC, known as APC (-)/CAP. The genetic predisposition to APC (-)/CAP has largely been associated with germline mutations in some susceptible genes, including the human mutY homologue (MUTYH) gene and the Nth-like DNA glycosylase 1 (NTHL1) gene, and DNA mismatch repair (MMR) can cause autosomal recessive APC (-)/CAP. Furthermore, autosomal dominant APC (-)/CAP could occur as a result of DNA polymerase epsilon (POLE)/DNA polymerase delta 1 (POLD1), axis inhibition protein 2 (AXIN2), and dual oxidase 2 (DUOX2) mutations. The clinical phenotypes of these pathogenic mutations vary greatly depending on their genetic characteristics. Therefore, in this study, we present a comprehensive review of the association between autosomal recessive and dominant APC (-)/CAP genotypes and clinical phenotypes and conclude that APC (-)/CAP is a disease caused by multiple genes with different phenotypes and interaction exists in the pathogenic genes.
Topics: Humans; Adenomatous Polyposis Coli; Mutation; Genetic Association Studies; Genetic Predisposition to Disease; Genotype; Germ-Line Mutation; Phenotype; Genes, APC
PubMed: 36862359
DOI: 10.1007/s10620-023-07890-9 -
The Journal of Pathology Jan 2016Murine models of intestinal cancer are powerful tools to recapitulate human intestinal cancer, understand its biology and test therapies. With recent developments... (Review)
Review
Murine models of intestinal cancer are powerful tools to recapitulate human intestinal cancer, understand its biology and test therapies. With recent developments identifying the importance of the tumour microenvironment and the potential for immunotherapy, autochthonous genetically engineered mouse models (GEMMs) will remain an important part of preclinical studies for the foreseeable future. This review will provide an overview of the current mouse models of intestinal cancer, from the Apc(Min/+) mouse, which has been used for over 25 years, to the latest 'state-of-the-art' organoid models. We discuss here how these models have been used to define fundamental processes involved in tumour initiation and the attempts to generate metastatic models, which is the ultimate cause of cancer mortality. Together these models will provide key insights to understand this complex disease and hopefully will lead to the discovery of new therapeutic strategies.
Topics: Adenocarcinoma; Adenomatous Polyposis Coli; Adenomatous Polyposis Coli Protein; Animals; Carcinogenesis; Colorectal Neoplasms; Disease Models, Animal; Forecasting; Genes, APC; Humans; Mice; Mice, Transgenic; Mutation; Neoplasm Metastasis; Neoplasm Transplantation
PubMed: 26414675
DOI: 10.1002/path.4645 -
Internal Medicine Journal May 2015Identifying individuals with a genetic predisposition to developing familial colorectal cancer (CRC) is crucial to the management of the affected individual and their...
Identifying individuals with a genetic predisposition to developing familial colorectal cancer (CRC) is crucial to the management of the affected individual and their family. In order to do so, the physician requires an understanding of the different gene mutations and clinical manifestations of familial CRC. This review summarises the genetics, clinical manifestations and management of the known familial CRC syndromes, specifically Lynch syndrome, familial adenomatous polyposis, MUTYH-associated neoplasia, juvenile polyposis syndrome and Peutz-Jeghers syndrome. An individual suspected of having a familial CRC with an underlying genetic predisposition should be referred to a familial cancer centre to enable pre-test counselling and appropriate follow up.
Topics: Adenomatous Polyposis Coli; Australia; Chemoprevention; Colorectal Neoplasms; Colorectal Neoplasms, Hereditary Nonpolyposis; Female; Genetic Counseling; Genetic Predisposition to Disease; Genetic Testing; Humans; Intestinal Polyposis; Male; Mutation; Neoplastic Syndromes, Hereditary; New Zealand; Peutz-Jeghers Syndrome; Prevalence
PubMed: 25955461
DOI: 10.1111/imj.12736 -
World Journal of Gastrointestinal... Mar 2015Colorectal cancer (CRC) is a major cause of morbidity and mortality around the world, and approximately 5% of them develop in a context of inherited mutations leading to... (Review)
Review
Colorectal cancer (CRC) is a major cause of morbidity and mortality around the world, and approximately 5% of them develop in a context of inherited mutations leading to some form of familial colon cancer syndromes. Recognition and characterization of these patients have contributed to elucidate the genetic basis of CRC. Polyposis Syndromes may be categorized by the predominant histological structure found within the polyps. The aim of the present paper is to review the most important clinical features of the Hamartomatous Polyposis Syndromes, a rare group of genetic disorders formed by the peutz-Jeghers syndrome, juvenil polyposis syndrome and PTEN Hamartoma Tumor Syndrome (Bannayan-Riley-Ruvalacaba and Cowden Syndromes). A literature search was performed in order to retrieve the most recent and important papers (articles, reviews, clinical cases and clinical guidelines) regarding the studied subject. We searched for terms such as "hamartomatous polyposis syndromes", "Peutz-Jeghers syndrome", "juvenile polyposis syndrome", "juvenile polyp", and "PTEN hamartoma tumour syndrome" (Cowden syndrome, Bananyan-Riley-Ruvalcaba). The present article reports the wide spectrum of disease severity and extraintestinal manifestations, with a special focus on their potential to develop colorectal and other neoplasia. In the literature, the reported colorectal cancer risk for Juvenile Polyposis, Peutz-Jeghers and PTEN Hamartoma Tumor Syndromes are 39%-68%, 39%-57% and 18%, respectively. A review regarding cancer surveillance recommendations is also presented.
PubMed: 25848489
DOI: 10.4240/wjgs.v7.i3.25 -
Gastroenterology Report 2023Bone morphogenetic protein receptor type 1A () is responsible for two individual Mendelian diseases: juvenile polyposis syndrome and hereditary mixed polyposis syndrome...
BACKGROUND
Bone morphogenetic protein receptor type 1A () is responsible for two individual Mendelian diseases: juvenile polyposis syndrome and hereditary mixed polyposis syndrome 2, which have overlapping phenotypes. This study aimed to elucidate whether these two syndromes are just two subtypes of a single syndrome rather than two isolated syndromes.
METHODS
We sequenced the gene in 186 patients with polyposis and colorectal cancer, and evaluated the clinicopathological features and phenotypes of the probands and their available relatives with mutations.
RESULTS
germline mutations were found in six probands and their three available relatives. The numbers of frameshift, nonsense, splice-site, and missense mutations were one, one, two, and two, respectively; two of the six mutations were novel. Typical juvenile polyps were found in only three patients. Two patients had colorectal cancer rather than any polyps.
CONCLUSIONS
Diseases in germline mutation carriers vary from mixed polyposis to sole colorectal cancer, and typical juvenile polyps do not always occur in these carriers. The variety of phenotypes reflected the features of -mutation carriers, which should be recognized as a spectrum of one syndrome. Genetic testing may be a good approach to identifying -related syndromes.
PubMed: 36632626
DOI: 10.1093/gastro/goac082