title: Telomere dysfunction and tumor suppression responses in dyskeratosis congenita: balancing cancer and tissue renewal impairment.
abstract: Dyskeratosis congenita (DC) encompasses a large spectrum of diseases and clinical manifestations generally related to premature aging, including bone marrow failure and cancer predisposition. The major risk factor for DC is to carry germline telomere-related mutations - in telomerase or telomere shelterin genes - which results in premature telomere dysfunction, thus increasing the risk of premature aging impairments. Despite the advances that have been accomplished in DC research, the molecular aspects underlying the phenotypic variability of the disease remain poorly understood. Here different aspects of telomere biology, concerning adult stem cells senescence, tumor suppression and cancer are considered in the context of DC, resulting in two translational models: late onset of DC symptoms in telomere-related mutations carriers is a potential indicator of increased cancer risk and differences in tumor suppression capacities among the genetic subgroups are (at least partial) causes of different clinical manifestations of the disease. The limitations of both models are presented, and further experiments for their validation, as well as clinical implications, are discussed.
authors.affiliation: Oncology Research Group, Technology Development Center (Biotechnology Unit), Federal University of Pelotas, University Campus, Building 19, Mail Box 354, Pelotas, RS 96010-900, Brazil. fernandophartwig@gmail.com
authors.forename: Fernando Pires
authors.initials: FP
authors.lastname: Hartwig
authors.forename: Tiago
authors.initials: T
authors.lastname: Collares
mesh_terms: D017668:Age of Onset; D000368:Aged; D019588:Aging, Premature / Q000209:etiology / Q000235:genetics; D001855:Bone Marrow Diseases / Q000209:etiology / Q000235:genetics; D016922:Cellular Senescence / Q000235:genetics; D019871:Dyskeratosis Congenita / Q000150:complications / Q000235:genetics / Q000503:physiopathology; D016147:Genes, Tumor Suppressor; D020022:Genetic Predisposition to Disease; D006801:Humans; D008962:Models, Theoretical; D009154:Mutation; D009369:Neoplasms / Q000209:etiology / Q000235:genetics; D012307:Risk Factors; D019098:Telomerase / Q000235:genetics*; D016615:Telomere / Q000235:genetics*; D059505:Telomere Homeostasis / Q000235:genetics*; D057170:Translational Research, Biomedical / Q000379:methods
chemical_list: D019098:Telomerase