title: InheritedTP53Mutations and the Li-Fraumeni Syndrome.
abstract: Li-Fraumeni syndrome (LFS) is a complex hereditary cancer predisposition disorder associated with early-onset cancers in diverse tissues of origin. GermlineTP53mutations are identified in 75% of patients with classic LFS. The lifetime likelihood of aTP53mutation carrier developing cancer approaches 75% in males and almost 100% in females. Several genetic modifiers have been implicated to account for the phenotypic variability within and across LFS families; however, efforts to develop predictive algorithms of age of onset and type of cancers in individual patients have not yet found clinical use. Although it is not possible to prevent cancers from forming in LFS patients, novel protocols have been developed for surveillance for early tumor detection, leading to improvements in survival. Comprehensive studies of the genome and epigenome in LFS families in the context of germlineTP53mutations is anticipated to shed light on this intriguing, yet devastating, disease and to transform the clinical management of patients.
authors.affiliation: Genetics and Genome Biology Program, The Hospital for Sick Children and Institute of Medical Science, University of Toronto, Toronto, Ontario M5G 1X8, Canada.
authors.forename: Tanya
authors.initials: T
authors.lastname: Guha
authors.affiliation: Division of Hematology/Oncology and Genetics and Genome Biology Program, The Hospital for Sick Children; Departments of Pediatrics and Medical Biophysics, University of Toronto, Toronto, Ontario M5G 1X8, Canada.
authors.forename: David
authors.initials: D
authors.lastname: Malkin
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D005190:Family; D020022:Genetic Predisposition to Disease; D018095:Germ-Line Mutation; D006801:Humans; D016864:Li-Fraumeni Syndrome / Q000235:genetics*; D051379:Mice; D016159:Tumor Suppressor Protein p53 / Q000235:genetics*
chemical_list: C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53