title: MUC gene abnormalities in sporadic and hereditary mucinous colon cancers with microsatellite instability.
abstract: Aim of this study was verifying whether mucin producing colon cancers (CRCs) could develop through a molecular pathway involving microsatellite instability (MSI) and MUC gene alterations. Out of 49 CRCs expressing variable amounts of mucin, 22 (44.9%) were MSI-H and 5 (10.2%) were MSI-L. MUC genes were analyzed by Southern blotting and extra bands were evident in the Variable Number Tandem Repetition (VNTR) regions of MUC2 (5 cases) and MUC5AC (2 cases), but not MUC1 and MUC4 genes. Since the somatic VNTR abnormalities were detected in 6 MSI-H and in 1 MSI-L tumors, they seem to be peculiar of mismatch repair defective CRCs. Our finding suggests that alteration and/or loss of structurally normal MUC genes may be an important step in the neoplastic molecular pathway of a subset of CRCs and that mutations involving VNTR repetitive sequences may exist in MSI tumors as a direct and/or indirect consequence of an inefficient MMR system.
authors.affiliation: Department of Preclinical Research and Epidemiology, Centro Riferimento Oncologico, IRCCS, Aviano (PN), Italy.
authors.forename: Chiara
authors.initials: C
authors.lastname: Pastrello
authors.forename: Manuela
authors.initials: M
authors.lastname: Santarosa
authors.forename: Mara
authors.initials: M
authors.lastname: Fornasarig
authors.forename: Roberto
authors.initials: R
authors.lastname: Sigon
authors.forename: Tiziana
authors.initials: T
authors.lastname: Perin
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Giannini
authors.forename: Mauro
authors.initials: M
authors.lastname: Boiocchi
authors.forename: Alessandra
authors.initials: A
authors.lastname: Viel
mesh_terms: D020137:Base Pair Mismatch; D015139:Blotting, Southern; D045744:Cell Line, Tumor; D003110:Colonic Neoplasms / Q000235:genetics* / Q000378:metabolism; D004260:DNA Repair; D043243:DNA Sequence, Unstable; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D018895:Microsatellite Repeats; D008957:Models, Genetic; D055271:Mucin 5AC; D018396:Mucin-1 / Q000235:genetics; D055262:Mucin-2; D055264:Mucin-4; D009077:Mucins / Q000235:genetics* / Q000378:metabolism; D009369:Neoplasms / Q000378:metabolism; D016133:Polymerase Chain Reaction
chemical_list: C524625:MUC2 protein, human; C524658:MUC4 protein, human; C524678:MUC5AC protein, human; D055271:Mucin 5AC; D018396:Mucin-1; D055262:Mucin-2; D055264:Mucin-4; D009077:Mucins