Fifty years after the recognition of the Li–Fraumeni syndrome (LFS), our perception of cancers related to germline alterations of TP53 has drastically changed: (i) germline TP53 alterations are often identified among children with cancers, in particular soft-tissue sarcomas, adrenocortical carcinomas, central nervous system tumours, or among adult females with early breast cancers, without familial history. This justifies the expansion of the LFS concept to a wider cancer predisposition syndrome designated heritable TP53-related cancer (hTP53rc) syndrome; (ii) the interpretation of germline TP53 variants remains challenging and should integrate epidemiological, phenotypical, bioinformatics prediction, and functional data; (iii) the penetrance of germline disease-causing TP53 variants is variable, depending both on the type of variant (dominant-negative variants being associated with a higher cancer risk) and on modifying factors; (iv) whole-body MRI (WBMRI) allows early detection of tumours in variant carriers and (v) in cancer patients with germline disease-causing TP53 variants, radiotherapy, and conventional genotoxic chemotherapy contribute to the development of subsequent primary tumours. It is critical to perform TP53 testing before the initiation of treatment in order to avoid in carriers, if possible, radiotherapy and genotoxic chemotherapies. In children, the recommendations are to perform clinical examination and abdominal ultrasound every 6 months, annual WBMRI and brain MRI from the first year of life, if the TP53 variant is known to be associated with childhood cancers. In adults, the surveillance should include every year clinical examination, WBMRI, breast MRI in females from 20 until 65 years and brain MRI until 50 years.

在认识到Li-Fraumeni综合征（LFS）五十年之后，我们对与TP53生殖系改变有关的癌症的认识已发生了巨大变化：（i）患有癌症的儿童（尤其是软组织肉瘤）中经常发现TP53发生了改变，没有家族史的肾上腺皮质癌，中枢神经系统肿瘤或患有早期乳腺癌的成年女性。这证明了将LFS概念扩展到更广泛的癌症易感综合症（称为遗传性TP53相关癌症（h TP53 rc）综合症）的合理性；（ii）种系TP53的解释变体仍然具有挑战性，应整合流行病学，表型，生物信息学预测和功能数据；（iii）引起种系疾病的TP53变异体的外在能力是可变的，这取决于变异体的类型（显性负变异体与较高的癌症风险相关）和修饰因子；（iv）全身MRI（WBMRI）可以及早发现变体携带者中的肿瘤，以及（v）患有种系疾病致病性TP53变体的癌症患者，放疗和常规遗传毒性化学疗法可促进后续原发性肿瘤的发展。进行TP53至关重要在治疗开始之前进行测试，以免在携带者中避免放射疗法和遗传毒性化学疗法。对于儿童，建议如果已知TP53变异与儿童癌症有关，则建议每6个月进行临床检查和腹部超声检查，并从出生后第一年开始每年进行WBMRI和脑MRI检查。在成年人中，监测应包括每年从20岁至65岁的女性进行的临床检查，WBMRI，乳腺MRI和至50岁的脑部MRI。