Abstract
Nonrandom aggregations of cancer have been recognized to occur for over 200 years. Although almost every type of cancer has been reported to occur in a familial form, evidence of hereditary and familial influences exists in less than 30% of cases. Li-Fraumeni syndrome (LFS) is a rare yet informative autosomal dominant multicancer predisposition syndrome. Our understanding of this disorder and the importance of molecular genetic events in the development of familial cancer has evolved through the evaluation of clinical observations, genetic epidemiology, and molecular biology of many of these affected kindreds. This article reviews the original and evolving clinical observations and definitions of LFS, the causal association attributed to germline TP53 gene mutations, and the genotype: phenotype aspects of the syndrome. The challenges of genetic heterogeneity are discussed, as well as the impact of predictive genetic testing and management; opportunities for application of research to future interventions are explored.
Original language | English |
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Title of host publication | Encyclopedia of Cancer |
Publisher | Elsevier |
Pages | 356-368 |
Number of pages | 13 |
ISBN (Electronic) | 9780128124857 |
DOIs | |
State | Published - 1 Jan 2018 |
Externally published | Yes |
Keywords
- Cancer predisposition syndrome
- Familial cancer
- Germline
- Hereditary cancer
- Li-Fraumeni syndrome
- Surveillance
- TP53
- Tumor suppressor gene