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Li-Fraumeni-Syndrom

  • Paul Kleihues
  • Hiroko Ohgaki
  • Pierre Hainaut
Part of the Molekulare Medizin book series (MOLMED)

Zusammenfassung

Das Li-Fraumeni-Syndrom (LFS) ist ein autosomal-dominant vererbtes,neoplastischesSyndrom und durch das Auftreten multipler Tumoren im Kindes- und frühen Erwachsenenalter charakterisiert. Bei den LFS-assoziierten Neoplasien handelt es sich in erster Linie um Brustkrebs, Weichteilsarkome und Knochensarkome sowie ein vermehrtes Auftreten von Hirntumoren, Leukämien und Karzinomen der Nebennierenrinde(Li u. Fraumeni 1969; Li et al. 1988). Die Mehrzahl der LFS-Patienten hat eine Keimbahnmutation im TP53-Tumorsuppressorgen (Malkin et al. 1990; Srivastava et al. 1990; Varley, et al. 1997). Bei einigen Familien, die die Kriterien des LFS oder von LFS-Varianten erfüllen, wurde eine heterozygote Keimbahnmutation des hCHK2-Gens nachgewiesen (Bell et al. 1999).

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Literatur

  1. Albrechtsen N, Dornreiter I, Grosse F, Kim E, Wiesmuller L, Deppert W (1999) Maintenance of genomic integrity by p53: complementary roles for activated and non-activated p53. Oncogene 18:7706–7717PubMedCrossRefGoogle Scholar
  2. Bell DW, Varley JM, Szydlo TE et al. (1999) Heterozygous germ line hCHK2 mutations in Li-Fraumeni syndrome. Science 286:2528–2531PubMedCrossRefGoogle Scholar
  3. Birch JM, Hartley AL, Blair V et al. (1990) Cancer in the families of children with soft tissue sarcoma. Cancer 66:2239–2248PubMedCrossRefGoogle Scholar
  4. Birch JM, Hartley AL, Tricker KJ et al. (1994) Prevalence and diversity of constitutional mutations in the p53 gene among 21 Li-Fraumeni families. Cancer Res 54:1298–1304PubMedGoogle Scholar
  5. Eng C, Schneider K, Fraumeni JF Jr, Li FP (1997) Third international workshop of collaborative interdisciplinary studies of p53 and other predisposing genes in Li-Fraumeni syndrome. Cancer Epidemiol Bio markers Prev 6:379–383Google Scholar
  6. Fritsche M, Haessler C, Brandne T G (1993) Induction of nuclear accumulation of the tumor-suppressor protein p53 by DNA-damaging agents. Oncogene 8:307–318PubMedGoogle Scholar
  7. Garber JE, Goldstein AM, Kantor AF, Dreyfus MG, Fraumeni JF Jr, Li FP (1991) Follow-up study of twenty-four families with Li-Fraumeni syndrome. Cancer Res 51:6094–6097PubMedGoogle Scholar
  8. Graeber TG, Peterson JF, Tsai M, Monica K, Fornace AJ Jr, Giaccia AJ (1994) Hypoxia induces accumulation of p53 protein, but activation of a G1-phase checkpoint by low-oxygen conditions is independent of p53 status. Mol Cell Biol 14:6264–6277PubMedCrossRefGoogle Scholar
  9. Hainaut P, Soussi T, Shomer B et al. (1997) Database of p53 gene somatic mutations in human tumors and cell lines: updated compilation and future prospects. Nucleic Acids Res 25:151–157PubMedCrossRefGoogle Scholar
  10. Harris CC (1996) The 1995 Walter Hubert Lecture — molecular epidemiology of human cancer: insights from the mu-tational analysis of the p53 tumour-suppressor gene. Br J Cancer 73:261–269PubMedCrossRefGoogle Scholar
  11. Kleihues P, Schäuble B, Hausen zur A, Esteve J, Ohgaki H (1997) Tumours associated with p53 germline mutations. Am J Pathol 150:1–13PubMedGoogle Scholar
  12. Knudson AG (1996) Hereditary cancer: two hits revisited. J Cancer Res Clin Oncol 122:135–140PubMedCrossRefGoogle Scholar
  13. Levine AJ (1997) p53, the cellular gatekeeper for growth and division. Cell 88:323–331PubMedCrossRefGoogle Scholar
  14. Li FP, Fraumeni JF Jr (1969) Soft-tissue sarcomas, breast cancer, and other neoplasms. A familial syndrome? Ann Intern Med 71:747–752Google Scholar
  15. Li FP, Fraumeni JF Jr, Mulvihill JJ et al. (1988) A cancer family syndrome in twenty-four kindreds. Cancer Res 48:5358–5362PubMedGoogle Scholar
  16. Malkin D, Li FP, Strong LC et al. (1990) Germ line p53 mutations in a familial syndrome of breast cancer, sarcomas, and other neoplasms. Science 250:1233–1238PubMedCrossRefGoogle Scholar
  17. Ohgaki H, Hernandez T, Kleihues P, Hainaut P (1998) The molecular basis of the Li-Fraumeni syndrome. In: Kurzrock R, Talpaz M (eds) Molecular biology in cancer medicine, 2nd edn. Martin Dunitz Publisher, pp 477–492Google Scholar
  18. Ohgaki H, Vital A, Kleihues P, Hainaut P (2000) Li-Fraumeni syndrome and TP53 germline mutations. In: Kleihues P, Cavenee WK (eds) World Health Organization Classification of Tumours. Pathology and genetics of tumours of the nervous system. IARC Press, Lyon, pp 231–234Google Scholar
  19. Reifenberger J, Janssen G, Weber RG et al. (1998) Primitive neuroectodermal tumors of the cerebral hemispheres in two siblings with TP53 germline mutation. J Neuropathol Exp Neurol 57:179–187PubMedCrossRefGoogle Scholar
  20. Sameshima Y, Tsunematsu Y, Watanabe S et al. (1992) Detection of novel germ-line p53 mutations in di verse-cancer-prone families identified by selecting patients with childhood adrenocortical carcinoma. J Natl Cancer Inst 84:703–707PubMedCrossRefGoogle Scholar
  21. Sodha N, Williams R, Mangion J, Bullock SL, Yuille MR, Eeles RA (2000) Screening hCHK2 for mutations. Science 289:359PubMedCrossRefGoogle Scholar
  22. Srivastava S, Zou ZQ, Pirollo K, Blattner WA, Chang EH (1990) Germ-line transmission of a mutated p53 gene in a cancer-prone family with Li-Fraumeni syndrome. Nature 348:747–749PubMedCrossRefGoogle Scholar
  23. Varley JM, Evans DG, Birch JM (1997) Li-Fraumeni syndrome — a molecular and clinical review. Br J Cancer 76:1–14PubMedCrossRefGoogle Scholar
  24. Vital A, Bringuier PP, Huang H et al. (1998) Astrocytomas and choroid plexus tumors in two families with identical p53 germline mutations. J Neuropathol ExpNeurol 57:1061–1069CrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2001

Authors and Affiliations

  • Paul Kleihues
    • 1
  • Hiroko Ohgaki
    • 1
  • Pierre Hainaut
    • 1
  1. 1.International Agency for Research on Cancer (IARC)LyonFrankreich

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