TP53 mutation and Li-Fraumeni syndrome

Abstract

Preeminent among human tumor suppressor genes in functionality and importance is TP53, reflected by its well-recognized characterization as guardian of the genome.1-5 TP53 is perhaps the most intensively studied human-cancer-associated oncoprotein, in keeping with its protean effects on critical cellular pathways, including transcriptional control of gene expression, cell cycle proliferation, DNA repair, apoptosis, and cellular maturation and differentiation.6-8 Mutational damage to TP53 is the single most common cancer DNA alteration, having been observed in more than 50% of all human cancers.9 Detection of TP53 mutation is now performed for several clinical indications including assessment of tumor biological aggressiveness, discrimination of tumor recurrence versus de novo cancer formation, determination of tumor anaplasia, and as part of a search for germline inherited mutational change associated with heightened cancer susceptibility.10,11 The emerging diagnostic and prognostic role attributed to TP53 mutation detection justifies testing in selected patients as part of the clinical molecular pathology workup of human cancer. © 2007 Springer Science+Business Media, LLC.