Pathogenic germline variants in the TP53 gene predispose to a wide range of cancers, known collectively as Li-Fraumeni syndrome (LFS). There has been much research aimed to identify genotype-phenotype correlations, that is, differences between variant location and/or effect and cancer spectrum. These correlations, should they exist, have potential to impact clinical management of carriers. Review of previously published studies showed a variety of study designs and inconsistency in reported findings. Here, we used pooled data from 427 TP53 carriers who had undergone multigene panel testing and 154 TP53 carriers identified by single-gene testing to investigate correlations between TP53 genotype (truncating variants, hotspot variants, other missense variants with dominant-negative effect, missense variants without dominant-negative effect) and a number of LFS-selected malignancies. Our results suggest that carriers of truncating and hotspot variants might be more likely to present with LFS cancers and have shorter time to first cancer diagnosis compared to carriers of other variant types. However, the differences observed were minor, and we conclude that there is currently insufficient evidence to consider location and/or molecular effect of pathogenic variants to assist with clinical management of TP53 carriers. Larger studies are necessary to confirm the correlations suggested by our analysis.

TP53基因的致病种系变异易感于多种癌症，这些癌症统称为Li-Fraumeni综合征（LFS）。已有许多研究旨在鉴定基因型与表型的相关性，即变异位置和/或效应与癌症谱之间的差异。这些关联（如果存在）可能会影响载体的临床管理。对先前发表的研究的回顾表明，各种研究设计和报告的发现不一致。从427个这里，我们使用汇总数据TP53运营商谁经历了多基因面板的测试和154个TP53由单基因检测鉴定携带者进行调查之间的相关性TP53基因型（截短变体，热点变体，具有显性负效应的其他错义变体，无显性负效应的错义变体）和许多LFS选择的恶性肿瘤。我们的结果表明，与其他变异类型的携带者相比，截短和热点变异的携带者可能更容易出现LFS癌症，并且首次诊断癌症的时间更短。但是，观察到的差异很小，我们得出的结论是，目前尚无足够的证据来考虑致病变体的位置和/或分子效应，以协助TP53携带者的临床管理。为了确认我们的分析建议的相关性，需要进行更大的研究。