Cancer Res Treat.  2024 Jan;56(1):334-341. 10.4143/crt.2023.794.

Clinical Features of Li-Fraumeni Syndrome in Korea

• Song R
• Kong SY
• Choi W
• Lee EG
• Woo J
• Han JH
• Lee S
• Kang HS
• Jung SY

• KMID: 2550348
• DOI: http://doi.org/10.4143/crt.2023.794

Abstract

Purpose
Li-Fraumeni syndrome (LFS) is a hereditary disorder caused by germline mutation in TP53. Owing to the rarity of LFS, data on its clinical features are limited. This study aimed to evaluate the clinical characteristics and prognosis of Korean patients with LFS.
Materials and Methods
Patients who underwent genetic counseling and confirmed with germline TP53 mutation in the National Cancer Center in Korea between 2011 and 2022 were retrospectively reviewed. Data on family history with pedigree, types of mutation, clinical features, and prognosis were collected.
Results
Fourteen patients with LFS were included in this study. The median age at diagnosis of the first tumor was 32 years. Missense and nonsense mutations were observed in 13 and one patients, respectively. The repeated mutations were p.Arg273His, p.Ala138Val, and pPro190Leu. The sister with breast cancer harbored the same mutation of p.Ala138Val. Seven patients had multiple primary cancers. Breast cancer was most frequently observed, and other types of tumor included sarcoma, thyroid cancer, pancreatic cancer, brain tumor, adrenocortical carcinoma, ovarian cancer, endometrial cancer, colon cancer, vaginal cancer, skin cancer, and leukemia. The median follow-up period was 51.5 months. Two and four patients showed local recurrence and distant metastasis, respectively. Two patients died of leukemia and pancreatic cancer 3 and 23 months after diagnosis, respectively.
Conclusion
This study provides information on different characteristics of patients with LFS, including types of mutation, types of cancer, and prognostic outcomes. For more appropriate management of these patients, proper genetic screening and multidisciplinary discussion are required.

Keyword

Li-Fraumeni syndrome; Germ-line mutation; Hereditary disease

Figure

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  Fig. 1. Comparison of pedigrees between patients with Li-Fraumeni syndrome. (A) A pedigree of patient 7 with only a family history of breast cancer. (B) A pedigree of patient 11 with a family history of various malignancies in first- or second-degree relatives and who met the Chompret criteria. Br, breast cancer; Cvx, cervical cancer; Lun, lung cancer; Mel, melanoma; Ov, ovarian cancer; Thy, thyroid cancer.

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  Fig. 2. Lollipop mutation diagram of the study population. All mutations shown in this study were at DNA-binding domain. Except for one patient with nonsense mutation in codon 213, other 13 patients showed missense mutations. A138V (n=2), P190L (n=2), and R273H (n=2) were repeated, and two patients with A138V mutation were sisters. A, alanine; H, histidine; L, leucine; P, proline; R, arginine; T, tryptophan; V, valine.

Reference

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