Li-Fraumeni syndrome – a case report
Abstract
Introduction. Li-Fraumeni syndrome (LFS) is a hereditary familial predisposition to a wide range of certain, often rare malignant diseases. Patients also have an increased risk of developing secondary and even tertiary malignancies throughout their lifetime. The most common malignancies are soft-tissue and bone sarcomas, breast cancer, brain tumors, adrenocortical carcinoma, and acute leukemia. The syndrome is inherited as an autosomal dominant disorder. In most families with LFS, germline mutations of the tumor protein have been identified on the TP53 gene. To our knowledge, this is the second case report of LFS that has been reported in our country so far. Case report. We present five members of the same family with malignant diseases typical for LFS. A woman at the age of 21 had recurrent astrocytoma and mediastinal liposarcoma. Her older sister had rhabdomyosarcoma and liver cancer and died at the age of 18. The mother of their father was diagnosed with breast cancer at the age of 45, and she died at the age of 52. The father’s sister had osteosarcoma and died before the age of 40. The father was diagnosed with lung adenocarcinoma at the age of 49, two years after the death of his second daughter. Genetic analysis identified a pathogenic, heterozygous germline mutation of the TP53 gene. He also has a third, 8-year-old daughter for whom he denied testing for LFS. Conclusion. Genetic analysis for LFS of all family members is required in patients with rare and multiple malignancies but also frequent and early onset malignancies in the family. Screening for the detection of early cancer manifestation is the key to prolonged survival in people with LFS.
References
1. Frebourg T, Bajalica LS, Oliveira C, Magenheim R, Evans DG. European Reference Network GENTURIS. Guidelines for the Li-Fraumeni and heritable TP53-related cancer syndromes. Eur J Hum Genet 2020; 28(10): 1379–86.
2. de Andrade KC, Frone MN, Wegman-Ostrosky T, Khincha PP, Kim J, Amadou A, et al. Variable population prevalence estimates of germline TP53 variants: a gnomAD-based analysis. Hum Mutat 2019; (40): 97–105.
3. Li FP, Fraumeni JF. Soft-tissue sarcomas, breast cancer, and other neoplasms – a familial syndrome? Ann Intern Med 1969; 71(4): 747‒52.
4. Malkin D, Garber JE, Strong LC, Friend SH. CANCER. The cancer predisposition revolution. Science 2016; 352(6289): 1052‒3.
5. Druker H, Zelley K, McGee RB, Scollon SR, Kohlmann WK, Schneider KA, et al. Genetic counselor recommendations for cancer predisposition evaluation and surveillance in the pediatric oncology patient. Clin Cancer Res 2017; 23(13): e91–e97.
6. Guha T, Malkin D. Inherited TP53 mutations and the Li-Fraumeni syndrome. Cold Spring Harb Perspect Med 2017; 7(4): a026187.
7. Kratz CP, Achatz MI, Brugieres L, Frebourg T, Garber JE, Greer MLC, et al. Cancer screening recommendations for individuals with Li-Fraumeni syndrome. Clin Cancer Res 2017; 23(11): e38‒e45.
8. Bakhuizen JJ, Velthuizen ME, Stehouwer S, Bleiker EM, Ausems MG. Genetic counselling of young women with breast cancer for Li-Fraumeni syndrome: a nationwide survey on the experiences and attitudes of genetics professionals. Fam Cancer 2019; 18(2): 231‒9.
9. Etzold A, Schröder JC, Bartsch O, Zechner U, Galetzka D. Further evidence for pathogenicity of the TP53 tetramerization domain mutation p.Arg342Pro in Li-Fraumeni syndrome. Fam Cancer 2015; 14(1): 161–5.
10. Macedo GS, Araujo Vieira I, Brandalize AP, Giacomazzi J, Inez Palmero E, Volc S. Rare germline variant (rs78378222) in the TP53 3′ UTR: evidence for a new mechanism of cancer predisposition in Li-Fraumeni syndrome. Cancer Genet 2016; 209(3): 97–106.
11. National Center for Biotechnology Information. ClinVar. Available from: https://www.ncbi.nlm.nih.gov/clinvar/variati
/>on/VCV000012369.
12. Louis DN, Ohgaki H, Wiestler OD, Cavenee WK. World Health Organization Histological Classification of Tumours of the Central Nervous System. Lyon, France: International Agency for Research on Cancer; 2016.
13. Detterbeck FC, Boffa DJ, Kim AV, Tanoue LT. The Eighth Edition Lung Cancer Stage Classification. Chest 2017; 151(1): 193–203.
14. Ettinger DS, Wood DE, Aisner DL, Akerley W, Bauman JR, Bharat A, et al. Non-Small Cell Lung Cancer, Version 3.2022, NCCN Clinical Practice Guidelines in Oncology. J Natl Compr Canc Netw 2022; 20(5): 497‒530.
15. van Persijn van Meerten EL, Gelderblom H, Bloem JL. RECIST revised: implications for the radiologist. A review article on the modified RECIST guideline. Eur Radiol 2010; 20(6): 1456‒67.
16. Oken MM, Creech RH, Tormey DC, Horton J, Davis TE, McFadden ET, et al. Toxicity and response criteria of the Eastern Cooperative Oncology Group. Am J Clin Oncol 1982; 5(6): 649‒55.
17. U.S. National Library of Medicine. ClinicalTrials.gov 2021. Treatment of Carrying TP53 Harmful Mutations in Advanced Refractory Solid Tumors. Identifier NCT03645200.