Molecular advances support the existence of an alternative pathway of colorectal carcinogenesis that is based on the hypermethylation of specific DNA regions that silences tumor suppressor genes. This alternative path...Molecular advances support the existence of an alternative pathway of colorectal carcinogenesis that is based on the hypermethylation of specific DNA regions that silences tumor suppressor genes. This alternative pathway has been called the serrated pathway due to the serrated appearance of tumors in histological analysis. New classifications for colorectal cancer(CRC) were proposed recently based on genetic profiles that show four types of molecular alterations: BRAF gene mutations, KRAS gene mutations, microsatellite instability, and hypermethylation of Cp G islands. This review summarizes what is known about the serrated pathway of CRC, including CRC molecular and clinical features, prognosis, and response to chemotherapy.展开更多
Hyperplastic polyps have traditionally been considered not to have malignant potential.New pathological classification of serrated polyps and recent discoveries about the serrated pathway of carcinogenesis have revolu...Hyperplastic polyps have traditionally been considered not to have malignant potential.New pathological classification of serrated polyps and recent discoveries about the serrated pathway of carcinogenesis have revolutionized the concepts and revitalized the research in this area.Until recently,it has been thought that most colorectal cancers arise from conventional adenomas via the traditional tumor suppressor pathway initiated by a mutation of the APC gene,but it has been found thatthis pathway accounts for only approximately 70%-80% of colorectal cancer(CRC)cases.The majority of the remaining colorectal cancer cases follow an alternative pathway leading to CpG island methylator phenotype carcinoma with BRAF mutation and with or without microsatellite instability.The mechanism of carcinomas arising from this alternative pathway seems to begin with an activating mutation of the BRAF oncogene.Serrated polyposis syndrome is a relatively rare condition characterized by multiple and/or large serrated polyps of the colon.Clinical characteristics,etiology and relationship of serrated polyposis syndrome to CRC have not been clarified yet.Patients with this syndrome show a high risk of CRC and both sporadic and hereditary cases have been described.Clinical criteria have been used for diagnosis and frequent colonoscopy surveillance should be performed in order to prevent colorectal cancer.In this review,we try to gather new insights into the molecular pathogenesis of serrated polyps in order to understand their possible clinical implications and to make an approach to the management of this syndrome.展开更多
文摘Molecular advances support the existence of an alternative pathway of colorectal carcinogenesis that is based on the hypermethylation of specific DNA regions that silences tumor suppressor genes. This alternative pathway has been called the serrated pathway due to the serrated appearance of tumors in histological analysis. New classifications for colorectal cancer(CRC) were proposed recently based on genetic profiles that show four types of molecular alterations: BRAF gene mutations, KRAS gene mutations, microsatellite instability, and hypermethylation of Cp G islands. This review summarizes what is known about the serrated pathway of CRC, including CRC molecular and clinical features, prognosis, and response to chemotherapy.
基金Supported by Grants from Instituto de Salud Carlos Ⅲ, INT09/208 and PI08/0726,to Jover RFundación de la CV para la Investigación en el Hospital General Universitario de Alicante, to Alenda C,Payá A and Jover R+1 种基金a predoctoral grant from Conselleria d'Educacióde la Generalitat Valenciana,VALi+d.EXP ACIF/2010/018,to Guarinos Ca grant from Fundación de la CV para la Investigación en el Hospital General Universitario de Alicante,to Rodríguez-Soler M
文摘Hyperplastic polyps have traditionally been considered not to have malignant potential.New pathological classification of serrated polyps and recent discoveries about the serrated pathway of carcinogenesis have revolutionized the concepts and revitalized the research in this area.Until recently,it has been thought that most colorectal cancers arise from conventional adenomas via the traditional tumor suppressor pathway initiated by a mutation of the APC gene,but it has been found thatthis pathway accounts for only approximately 70%-80% of colorectal cancer(CRC)cases.The majority of the remaining colorectal cancer cases follow an alternative pathway leading to CpG island methylator phenotype carcinoma with BRAF mutation and with or without microsatellite instability.The mechanism of carcinomas arising from this alternative pathway seems to begin with an activating mutation of the BRAF oncogene.Serrated polyposis syndrome is a relatively rare condition characterized by multiple and/or large serrated polyps of the colon.Clinical characteristics,etiology and relationship of serrated polyposis syndrome to CRC have not been clarified yet.Patients with this syndrome show a high risk of CRC and both sporadic and hereditary cases have been described.Clinical criteria have been used for diagnosis and frequent colonoscopy surveillance should be performed in order to prevent colorectal cancer.In this review,we try to gather new insights into the molecular pathogenesis of serrated polyps in order to understand their possible clinical implications and to make an approach to the management of this syndrome.