Li Fraumeni Syndrome

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Classification according to ICD-11
2B51.Y Osteosarcoma of bone and articular cartilage of other specified sites
ICD-11 ( WHO version 2019)

The Li-Fraumeni syndrome is an autosomal - dominant inherited disease with multiple tumors associated which often occur early in life. The disease is very rare; it is named after its first descriptions, Frederick P. Li and Joseph F. Fraumeni .

Disease emergence

The syndrome is often caused by a germline mutation of a tumor suppressor , the TP53 gene ( chromosome 17 gene locus p13.1), which codes for the p53 protein . The risk of developing cancer at the age of 30 is 50% and is therefore significantly higher than that of the general population (1%). Tumors associated with Li Fraumeni syndrome include soft tissue sarcomas , breast cancer , bone sarcomas , leukemia , astrocytomas , plexus carcinomas and carcinomas of the adrenal cortex . An increased incidence of lung cancer , tumors of the stomach and intestines , ovarian cancer and lymphoma was also observed in affected families . Since no mutation of the TP53 gene can be found in about 30% of those affected, defects in the p53 signal transduction pathway that have not yet been discovered are discussed as further triggers. Diseases associated with mutations in the CHEK2 gene have been referred to as Li-Fraumeni syndrome 2 . Another locus was recently identified on chromosome 1 .

diagnosis

Since only about 70% of patients have a detectable mutation in the TP53 gene, the diagnosis is made on the basis of clinical presentation. The following criteria must be met in order to diagnose Li-Fraumeni syndrome:

  • Patient with sarcoma before the age of 45 plus
  • At least one first-degree relative developed cancer before age 45 or developed sarcoma in the course of his life

In addition to the Li-Fraumeni syndrome in the narrower sense, a Li-Fraumeni-like syndrome has also been defined, in which, however, a TP53 mutation can be detected much less often. This is clinically defined as follows:

  • Patients with childhood tumors, sarcoma, brain tumors or adrenal tumors before the age of 45 plus
  • a first- or second-degree relative developed a tumor associated with Li-Fraumeni syndrome at any age plus
  • another first or second degree relative developed some tumor before he was 60 years old.

Li Fraumeni syndrome 2 is diagnosed by the following criteria:

  • three independent primary tumors in one person, one before the age of 45
  • a childhood tumor
  • a tumor of the Li Fraumeni tumor spectrum before the age of 45
  • a first- or second-degree relative with a tumor from the LF tumor spectrum and another relative with any tumor disease before the age of 60

Therapeutic approaches

In order to detect newly developing tumors as early as possible, close-knit examinations are necessary. A therapeutic approach could be the introduction of non-mutated TP53 DNA into the tumor cells. Here are adenoviruses used for the genetic material in the tumor cells insert. After successful individual healing attempts, the drug Advexin is available on a compassionate use basis for patients with Li-Fraumeni syndrome via a European subsidiary of the manufacturer Introgen .

Web links

References

  1. ^ FP Li, JF Fraumeni Jr.Soft-tissue sarcomas, breast cancer and other neoplasms: a familial syndrome? Ann Intern Med 1969; 71, pp. 747-752. PMID 5360287
  2. ↑ Srivastava et al .: Germ-line transmission of a mutated p53 gene in a cancer-prone family with Li-Fraumeni syndrome. Nature . 1990; 348, pp. 747-749 PMID 2259385
  3. ↑ Strong et al.: Cancer in survivors of childhood soft tissue sarcoma and their relatives. J Natl Cancer Inst 1987; 79, pp. 1213-1220, PMID 3480372
  4. ↑ Nichols et al .: Germ-line p53 mutations predispose to a wide spectrum of early-onset cancers. Cancer Epidemiol Biomarkers Prev . 2001; 10, pp. 83-87 PMID 11219776
  5. ↑ Bell et al: Heterozygous germ line hCHK2 mutations in Li-Fraumeni syndrome. Science . 1999; 286 (5449), pp. 2528-2531. PMID 10617473
  6. ↑ Bachinski et al .: Genetic mapping of a third Li-Fraumeni syndrome predisposition locus to human chromosome 1q23 . Cancer Res 2005; 65, pp. 427-431 PMID 15695383
  7. ↑ Varley et al .: Germ-line mutations of TP53 in Li-Fraumeni families: an extended study of 39 families. Cancer Res 1997; 57, pp. 3245-3252 PMID 9242456 .
  8. ↑ Medical Genetic Center Munich  ( page no longer available , search in web archives )  Info: The link was automatically marked as defective. Please check the link according to the instructions and then remove this notice.@1@ 2Template: Toter Link / mgz-muenchen.de  
  9. ↑ Hisada et al.: Multiple Primary Cancers in Families with Li-Fraumeni Syndrome , J Natl Cancer Inst. 1998; 90 (8), pp. 606-611 PMID 9554443
  10. ↑ Senzer et al .: p53 therapy in a patient with Li-Fraumeni syndrome. Mol Cancer Ther 2007; 6 (5), pp. 1478-1482 PMID 17483435
  11. ↑ Manufacturer's information on therapy with Advexin