title: Modeling chromosomal instability and epithelial carcinogenesis in the telomerase-deficient mouse.
abstract: Human carcinomas are intimately linked to advancing age. These cancers have complex cytogenetic profiles, including aneuploidy and chromosomal structural aberrations. While aged humans sustain a high rate of carcinomas, mice bearing common tumor suppressor gene mutations typically develop soft tissue sarcomas and lymphomas. One marked species distinction between human and mouse that bears on the predisposition to carcinogenesis lies in the radical differences in length and regulation of the telomere, nucleoprotein complexes that cap the ends of eukaryotic chromosomes. Recent cancer modeling studies in the telomerase knockout p53 mutant mice revealed that telomere dynamics might be relevant to carcinogenesis. In these mice, there is a shift in the tumor spectrum towards epithelial carcinomas, and these cancers emerge with complex cytogenetic profiles classical for human carcinomas. In this review, we suggest that the mechanism of fusion-bridge-breakage-translocation, triggered by critically short telomeres, may be one of the generators of genomic instability commonly seen in human carcinomas.
authors.affiliation: Department of Adult Oncology, Dana-Farber Cancer Institute, 44 Binney St., Boston, MA 02115, USA.
authors.forename: S
authors.initials: S
authors.lastname: Chang
authors.forename: C
authors.initials: C
authors.lastname: Khoo
authors.forename: R A
authors.initials: RA
authors.lastname: DePinho
mesh_terms: D000818:Animals; D002471:Cell Transformation, Neoplastic; D002875:Chromosomes; D004195:Disease Models, Animal; D016678:Genome; D006801:Humans; D051379:Mice; D018345:Mice, Knockout; D012878:Skin Neoplasms / Q000235:genetics* / Q000473:pathology; D019098:Telomerase / Q000235:genetics*; D016615:Telomere
chemical_list: D019098:Telomerase