Division of Clinical Cancer Genetics, Department of Pediatrics, City of Hope, Duarte, CA, USA.
Mol Diagn Ther. 2013 Feb;17(1):31-47. doi: 10.1007/s40291-013-0020-0.
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.
作为癌症中一种常见的获得性异常，肿瘤蛋白 p53（TP53）作为种系突变的作用仍在不断发展。种系 TP53 突变的临床影响通常是显著的，并影响整个生命周期，倾向于在儿童期罕见肿瘤和成年期意外早发的多种常见癌症。在本文中，我们回顾了 TP53 肿瘤抑制基因种系突变对当前医疗保健实践的临床相关性，包括识别 Li-Fraumeni 综合征（LFS）患者的最佳方法，识别与 LFS 相关的核心癌症，以及制定早期检测 LFS 相关肿瘤的策略。还回顾了几种针对 TP53 的方法，以改善 LFS 患者的预后。通过一个案例报告，突出了在当前快速发展的基因组技术时代，与遗传检测决策相关的特殊 TP53 检测困境和独特挑战。
