Li-Fraumeni综合征(LFS)是一种遗传性癌症易感性综合征,并且大多数LFS患者已被鉴定为p53肿瘤抑制基因(TP53)中的种系变异。在过去的三十年里,日本已经发表了大量TP53种系变异的病例报告。据我们所知,没有针对日本LFS患者的大规模研究.在这项研究中,我们旨在鉴定TP53种系变异的日本患者,并揭示日本LFS的特征.我们通过回顾医学文献和作者机构诊断的病例来收集报告的病例。我们从48个家族中鉴定了68个具有TP53种系致病性或可能的致病性变体的个体。48个家庭中,35(72.9%)有错义变体,其中大部分位于DNA结合环内。在68个受影响的个体中鉴定出总共128个肿瘤。128个肿瘤部位如下:乳腺,25;骨头,16;大脑,12;血液学,11;软组织,10;胃,10;肺,10;结肠直肠,10;肾上腺,9;肝脏,4;和其他人,11.与法国大型国家LFS队列研究相比,日本显示了LFS的独特表型模式。最重要的是,在日本TP53种系变异携带者中观察到胃癌患者的发病率较高.这些结果可能为日本LFS的临床管理提供有用的信息。
Li-Fraumeni syndrome (LFS) is a hereditary cancer predisposition syndrome, and the majority of patients with LFS have been identified with germline variants in the p53 tumor suppressor (TP53) gene. In the past three decades, considerable case reports of TP53 germline variants have been published in Japan. To the best of our knowledge, there have been no large-scale studies of Japanese patients with LFS. In this study, we aimed to identify Japanese patients with TP53 germline variants and to reveal the characteristics of LFS in Japan. We collected reported cases by reviewing the medical literature and cases diagnosed at the institutions of the authors. We identified 68 individuals from 48 families with TP53 germline pathogenic or likely pathogenic variants. Of the 48 families, 35 (72.9%) had missense variants, most of which were located within the DNA-binding loop. A total of 128 tumors were identified in the 68 affected individuals. The 128 tumor sites were as follows: breast, 25; bones, 16; brain, 12; hematological, 11; soft tissues, 10; stomach, 10; lung, 10; colorectum, 10; adrenal gland, 9; liver, 4; and others, 11. Unique phenotype patterns of LFS were shown in Japan in comparison to those in a large national LFS cohort study in France. Above all, a higher frequency of patients with stomach cancer was observed in Japanese TP53 germline variant carriers. These results may provide useful information for the clinical management of LFS in Japan.