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MUTYH-Associated Polyposis
Published in Dongyou Liu, Handbook of Tumor Syndromes, 2020
MUTYH-associated polyposis (MAP) represents an autosomal recessive form of intestinal polyposis that predisposes patients to colorectal cancer as well as extracolonic neoplasms. Clinically, MAP resembles AFAP (a milder form of FAP) in terms of polyp number and onset age. However, MAP differs from AFAP genetically by having biallelic (homozygous or compound heterozygous) mutations in the base excision repair gene MUTYH, instead of germline mutations in the APC gene (Table 21.1) [54,59]. Compared to patients harboring biallelic MUTYH mutations, those carrying monoallelic MUTYH mutations have a somewhat lower risk of developing colorectal cancer and other malignancies. Diagnosis of MAP is dependent on observation of typical clinical symptoms and application of molecular tests for mutations in MUTYH gene provides additional confirmation of this rare disorder. Given the lack of a specific cure, treatment options for MAP consist of symptomatic management (e.g., surgical resection of gastrointestinal polyps) in combination with regular surveillance.
Colorectal cancer syndromes
Published in Angus Clarke, Alex Murray, Julian Sampson, Harper's Practical Genetic Counselling, 2019
Other forms of polyposis include the following. Peutz-Jeghers syndrome (autosomal dominant): This is characterised externally by circumoral pigment spots as well as by polyps and neoplasms, which may occur throughout the gastrointestinal tract and also increase risks for extra-intestinal malignancy including breast and testicular cancers. The risk of malignancy is lower than in polyposis coli but is considerable and less preventable owing to the wider distribution of lesions. Most cases are associated with inherited mutations in LKB1/STK11.Juvenile polyposis syndrome (autosomal dominant): This is characterised by occurrence of hamartomatous gastrointestinal polyps and increased colorectal cancer risk. It is caused by pathogenic mutations in SMAD4 or BMPR1A.MutYH-associated polyposis (MAP) (autosomal recessive): This is associated with attenuated polyposis and colorectal cancer due to defects in the DNA repair gene MutYH. This disorder is of considerable significance, since it means that one can no longer assume that all familial colorectal cancers and polyposis are dominantly inherited.
Molecular Biology in Colorectal Adenoma and Adenocarcinoma
Published in Peter Sagar, Andrew G. Hill, Charles H. Knowles, Stefan Post, Willem A. Bemelman, Patricia L. Roberts, Susan Galandiuk, John R.T. Monson, Michael R.B. Keighley, Norman S. Williams, Keighley & Williams’ Surgery of the Anus, Rectum and Colon, 2019
The MutYH gene encodes for a protein that removes the product of oxidative damage to guanine, another form of DNA repair. Individuals who have inherited two mutated copies of this gene develop a somewhat attenuated form of adenomatous polyposis (MutYH associated polyposis [MAP]) with a very high lifetime risk of colorectal cancer, and considerable phenotypic overlap with FAP.23
Triumph against cancer: invading colorectal cancer with nanotechnology
Published in Expert Opinion on Drug Delivery, 2021
Preksha Vinchhi, Mayur M. Patel
Approximately, 70–80% of CRCs are sporadic which typically results from mutations that affect Wnt/β catenin signaling pathway. Remaining 20–30% of CRC cases account for hereditary CRC which includes hereditary nonpolyposis CRC/Lynch syndrome (2–4%), familial adenomatous polyposis (FAP) (1%) and MUTYH associated polyposis (MAP) (1%). Lynch syndrome is caused because of mutation in the genes involved in DNA mismatch repair, e.g. MutL homolog 1(MLH 1), MutS protein homolog 2(MSH 2), MutS protein homolog 6 (MSH 6), Mismatch repair endonuclease (PMS2) and epithelial cell adhesion molecule (EpCAM). Whereas FAP is caused by mutations in adenomatous polyposis coli (APC – a tumor suppressor gene). Juvenile polyposis, peutz jeghers disease, muir torre syndrome, Cowden disease are some of the rare hereditary syndromes [13].
Proteogenomic biomarkers in colorectal cancers: clinical applications
Published in Expert Review of Proteomics, 2020
Margherita Binetti, Augusto Lauro, Samuele Vaccari, Maurizio Cervellera, Valeria Tonini
In this setting, biological biomarkers could be used to differentiate between sporadic and hereditary cancer [5]. Among hereditary conditions, different elements have been described, such as the Familial Adenomatous Polyposis (FAP), and the Hereditary Non-Polyposis Colon Cancer (HNPCC), also known as Lynch Syndrome [48]. The FAP is an autosomal disorder, involving the APC gene, part of Wnt/beta-catenin pathway [49], while the Lynch Syndrome is the most frequent syndromic disease associated with CRC, representing 3% of new diagnoses [50]. It is a genetic condition due to DNA mismatch repair (MMR), expressed by few gene mutations responsible for error accumulation in DNA. In specific, the MLH1 gene (50%), MSH2 (40%), MSH6 genes (7%–10%), and PMS2 gene (5%) are often involved [5]. Finally, the PJS is also related to an increased cancer risk, which has been related to P53 pathway. The P53 activity test could be useful in the clinical management of the disease [51]. There are also some other inherited syndromes, such as MUTYH-associated polyposis and Cowden/PTEN hamartoma syndrome [52].
Role of immune checkpoint inhibitors in the treatment of colorectal cancer: focus on nivolumab
Published in Expert Opinion on Biological Therapy, 2019
Alexandre A. Jácome, Cathy Eng
Germline mutations in one of the several MMR genes occur in Lynch syndrome, also called hereditary nonpolyposis CRC (HNPCC) [65]. The other inherited patterns of CRC are not involved with MMR genes. These are involved with APC gene, and form the polyposis syndromes: familial adenomatous polyposis (FAP), MUTYH-associated polyposis (MAP), and the hamartomatous polyposis syndromes (Peutz-Jeghers, juvenile polyposis, Cowden syndrome) [66]. A less understood pattern is familial CRC, estimated to be present in 25% of patients [67]. These patients have family history of CRC, but they do not have an inherited identified genetic mutation, and do not have a pattern consistent with one of the inherited syndromes.