TP53 Gene and Li-Fraumeni Syndrome

ABSTRACT

Cancer is a disease that strikes most families and itsdevastating effects bring suffering and instability to bothpatient and family. Clustering of cancers in certainfamilies is even more devastating, leading medicine tostudy its origin and ways to prevent it. Many cancersyndromes have been identified due to the repeatedoccurrence of specific tumors over a certain age-range.The rare cancer predisposition Li-Fraumeni syndrome(OMIM #151623; LFS) is transmitted in an autosomaldominant pattern, which predisposes affectedindividuals to an increased risk of developing a varietyof cancers at an early age, including childhood. The mostcharacteristic forms of cancers in LFS include soft-tissuesarcoma, breast cancers, brain tumors, and adrenocorticalcarcinomas. LFS is a dominantly inherited syndrome,frequently associated with germline mutations in theTP53 gene (OMIM #191170), which encodes protein p53.This protein regulates cell cycle, apoptosis, DNA repair,differentiation, senescence and development. Activationof p53 prevents DNA replication and cell proliferationwhen cells are subjected to stress that may disturb geneticor genomic integrity. Thus, TP53 acts as a major tumorsuppressor gene by exerting simultaneous control onmany components of the molecular mechanisms ofcarcinogenesis. Loss of p53 function may favor cancerdevelopment and explains predisposition in germlineTP53 mutation carriers. This review will discuss the maincharacteristics of TP53, its regulation, the consequencesof its inactivation in cancer, the germline TP53 mutationrelated to Li-Fraumeni syndrome and strategies forsurveillance.