Characteristics of Li‐Fraumeni syndrome in Japan: A review study by the special committee of JSHT

Abstract

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 with 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.

A case of sequential medical therapy for advanced ureteral cancer in Li–Fraumeni syndrome

“…The median age of adrenocortical cancer onset was 3 years old (range: 0-31 years old). 5 Fig. 1 Schematic presentation of the clinical history for various malignancies in this case.…”

Case Report : Li-Fraumeni Syndrome with Central Nervous System Tumors in Two Siblings

“…But with LFS, CPC are the classic brain tumor, glioma and medulloblastoma are also relevant to LFS [ 12 ]. In addition, A review study about Characteristics of LFS in Japan pointed out that Children with CPC of the brain and ACC were reported to have a high likelihood of carrying a TP53 germline variant, even in the absence of any family history [ 13 ]. Because in the early stage of the disease, the family members of the child denied the relevant family history of the tumor.…”

Hereditary gynecologic tumors and precision cancer medicine

“…A higher frequency of gastric cancer has been observed in Japanese patients, and ethnicity may need to be considered in the clinical management of LFS. 109 The penetration rate is very high, at almost 100% in natal females. 110,111 Current NCCN guidelines state that the GPV of TP53 does not increase OC risk 45 ; nevertheless, if individuals with LFS develop gynecologic cancer, special care must be taken in testing and treatment selection, as approximately half develop multiple cancers simultaneously or at different times 110 Furthermore, there is a theoretical possibility that exposure to radiation induces the development of a second cancer, and diagnostic and therapeutic radiation should be avoided whenever possible.…”

“…Core LFS tumors (breast cancer, osteosarcoma, soft tissue sarcoma, brain tumors, and adrenocortical carcinoma) occur frequently, but all types, including hematologic, epithelial, and pediatric cancers, can occur. A higher frequency of gastric cancer has been observed in Japanese patients, and ethnicity may need to be considered in the clinical management of LFS 109 . The penetration rate is very high, at almost 100% in natal females 110,111 …”