Tumor protein p53 (TP53) testing and Li-Fraumeni syndrome : current status of clinical applications and future directions.
Prevalent as an acquired abnormality in cancer, the role of tumor protein p53 (TP53) as a germline mutation continues to evolve. The clinical impact of a germline TP53 mutation is often dramatic and affects the full life course, with a propensity to develop rare tumors in childhood and multiple common cancers of unexpectedly early onset in adulthood. In this article, we review the clinical relevance of germline mutations in the TP53 tumor suppressor gene to current healthcare practice, including the optimal ways to identify patients with Li-Fraumeni syndrome (LFS), to recognize the core cancers associated with LFS, and to develop strategies for early detection of LFS-associated tumors. Several TP53-targeted approaches to improve outcomes in LFS patients are also reviewed. A case report is used to highlight special TP53 testing dilemmas and unique challenges associated with genetic testing decisions in the current age of rapidly advancing genomic technologies.
Division of Clinical Cancer Genetics, Department of Pediatrics, City of Hope, Duarte, CA, USA. asorrell@coh.org
April D
AD
Sorrell
Carin R
CR
Espenschied
Julie O
JO
Culver
Jeffrey N
JN
Weitzel
D000306:Adrenal Cortex Neoplasms / Q000235:genetics; D001932:Brain Neoplasms / Q000235:genetics; D001943:Breast Neoplasms / Q000235:genetics; D005260:Female; D016158:Genes, p53; D056726:Genetic Association Studies / Q000379:methods; D005820:Genetic Testing / Q000379:methods*; D018095:Germ-Line Mutation; D006801:Humans; D016864:Li-Fraumeni Syndrome / Q000175:diagnosis* / Q000235:genetics; D010375:Pedigree; D012509:Sarcoma / Q000235:genetics; D016159:Tumor Suppressor Protein p53 / Q000032:analysis* / Q000235:genetics
C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53