{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T09:40:50Z","timestamp":1790674850213,"version":"4.1.0"},"reference-count":509,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2018,4,13]],"date-time":"2018-04-13T00:00:00Z","timestamp":1523577600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Medical Sciences"],"abstract":"<jats:p>Colon cancer is the third most common cancer worldwide. Most colorectal cancer occurrences are sporadic, not related to genetic predisposition or family history; however, 20\u201330% of patients with colorectal cancer have a family history of colorectal cancer and 5% of these tumors arise in the setting of a Mendelian inheritance syndrome. In many patients, the development of a colorectal cancer is preceded by a benign neoplastic lesion: either an adenomatous polyp or a serrated polyp. Studies carried out in the last years have characterized the main molecular alterations occurring in colorectal cancers, showing that the tumor of each patient displays from two to eight driver mutations. The ensemble of molecular studies, including gene expression studies, has led to two proposed classifications of colorectal cancers, with the identification of four\/five non-overlapping groups. The homeostasis of the rapidly renewing intestinal epithelium is ensured by few stem cells present at the level of the base of intestinal crypts. Various experimental evidence suggests that colorectal cancers may derive from the malignant transformation of intestinal stem cells or of intestinal cells that acquire stem cell properties following malignant transformation. Colon cancer stem cells seem to be involved in tumor chemoresistance, radioresistance and relapse.<\/jats:p>","DOI":"10.3390\/medsci6020031","type":"journal-article","created":{"date-parts":[[2018,4,13]],"date-time":"2018-04-13T14:38:14Z","timestamp":1523630294000},"page":"31","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":201,"title":["Colorectal Cancer: Genetic Abnormalities, Tumor Progression, Tumor Heterogeneity, Clonal Evolution and Tumor-Initiating Cells"],"prefix":"10.3390","volume":"6","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7900-8942","authenticated-orcid":false,"given":"Ugo","family":"Testa","sequence":"first","affiliation":[{"name":"Department of Hematology, Oncology and Molecular Medicine, Istituto Superiore di Sanit\u00e0, 00161 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elvira","family":"Pelosi","sequence":"additional","affiliation":[{"name":"Department of Hematology, Oncology and Molecular Medicine, Istituto Superiore di Sanit\u00e0, 00161 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Germana","family":"Castelli","sequence":"additional","affiliation":[{"name":"Department of Hematology, Oncology and Molecular Medicine, Istituto Superiore di Sanit\u00e0, 00161 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2018,4,13]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"274","DOI":"10.1016\/j.cell.2013.07.004","article-title":"The intestinal crypt, a prototype stem cell compartment","volume":"154","author":"Clevers","year":"2013","journal-title":"Cell"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1856","DOI":"10.1101\/gad.1674008","article-title":"The intestinal stem cell","volume":"22","author":"Barker","year":"2008","journal-title":"Genes Dev."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"146","DOI":"10.1016\/j.cell.2012.02.042","article-title":"The pan-ErbB negative regulator Lrig1 an intestinal stem cells marker that functions as a tumor suppressor","volume":"49","author":"Powell","year":"2012","journal-title":"Cell"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"618","DOI":"10.1038\/nm.2695","article-title":"Functional engraftment of colon epithelium expanded in vitro from a single adult Lgr5+ stem cell","volume":"18","author":"Yui","year":"2012","journal-title":"Nat. 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