title: The molecular landscape of colitis-associated carcinogenesis.
abstract: In spite of the well-established histopathological phenotyping of IBD-associated preneoplastic and neoplastic lesions, their molecular landscape remains to be fully elucidated. Several studies have pinpointed the initiating role of longstanding/relapsing inflammatory insult on the intestinal mucosa, with the activation of different pro-inflammatory cytokines (TNF-α, IL-6, IL-10, IFN-γ), chemokines and metabolites of arachidonic acid resulting in the activation of key transcription factors such as NF-κB. Longstanding inflammation may also modify the intestinal microbiota, prompting the overgrowth of genotoxic microorganisms, which may act as further cancer promoters. Most of the molecular dysregulation occurring in sporadic colorectal carcinogenesis is documented in colitis-associated adenocarcinoma too, but marked differences have been established in both their timing and prevalence. Unlike sporadic cancers, TP53 alterations occur early in IBD-related carcinogenesis, while APC dysregulation emerges mainly in the most advanced stages of the oncogenic cascade. From the therapeutic standpoint, colitis-associated cancers are associated with a lower prevalence of KRAS mutations than the sporadic variant. Epigenetic changes, including DNA methylation, histone modifications, chromatin remodeling, and non-coding RNAs, are significantly involved in colitis-associated cancer development and progression. The focus now is on identifying diagnostic and prognostic biomarkers, with a view to ultimately designing patient-tailored therapies.
authors.affiliation: Department of Medicine (DIMED), Surgical Pathology & Cytopathology Unit, University of Padua, Padua, Italy.
authors.forename: Deborah
authors.initials: D
authors.lastname: Saraggi
authors.affiliation: Department of Medicine (DIMED), Surgical Pathology & Cytopathology Unit, University of Padua, Padua, Italy.
authors.forename: Matteo
authors.initials: M
authors.lastname: Fassan
authors.affiliation: Department of Surgical Oncology and Gastroenterology (DiSCOG), Gastroenterology Unit, University of Padua, Padua, Italy.
authors.forename: Claudia
authors.initials: C
authors.lastname: Mescoli
authors.affiliation: Istituto Oncologico Veneto, IOV-IRCCS, Surgical Oncology Unit, Padua, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Scarpa
authors.affiliation: Department of Molecular Pathology, The Institute of Cancer Research, London, UK; Department of Medicine, The Royal Marsden NHS Trust, London, UK.
authors.forename: Nicola
authors.initials: N
authors.lastname: Valeri
authors.affiliation: Department of Surgical Oncology and Gastroenterology (DiSCOG), Gastroenterology Unit, University of Padua, Padua, Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Michielan
authors.affiliation: Department of Surgical Oncology and Gastroenterology (DiSCOG), Gastroenterology Unit, University of Padua, Padua, Italy.
authors.forename: Renata
authors.initials: R
authors.lastname: D'Incá
authors.affiliation: Department of Medicine (DIMED), Surgical Pathology & Cytopathology Unit, University of Padua, Padua, Italy. Electronic address: massimo.rugge@unipd.it.
authors.forename: Massimo
authors.initials: M
authors.lastname: Rugge
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D025601:Adenomatous Polyposis Coli Protein / Q000235:genetics; D015415:Biomarkers; D063646:Carcinogenesis / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D018925:Chemokines / Q000378:metabolism; D003092:Colitis / Q000473:pathology*; D003093:Colitis, Ulcerative / Q000473:pathology*; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D016207:Cytokines / Q000378:metabolism; D019175:DNA Methylation; D018450:Disease Progression; D044127:Epigenesis, Genetic; D006801:Humans; D007413:Intestinal Mucosa / Q000473:pathology; D011230:Precancerous Conditions / Q000235:genetics*; D016283:Proto-Oncogene Proteins p21(ras) / Q000235:genetics; D016159:Tumor Suppressor Protein p53 / Q000235:genetics
chemical_list: C555337:APC protein, human; D025601:Adenomatous Polyposis Coli Protein; D015415:Biomarkers; D018925:Chemokines; D016207:Cytokines; C117307:KRAS protein, human; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; D016283:Proto-Oncogene Proteins p21(ras)
keywords: Biomarkers; Colitis; Dysplasia; IBD; Molecular pathology