Li-Fraumeni Syndrome – a Proposal of Complex Prevention Care for Carriers of TP53 Mutation with Total-Body MRI

Czech version

Authors: L. Foretová ¹; J. Štěrba ⁴; P. Opletal ³; V. Mach ⁵; J. Lisý ⁸; K. Petrakova ²; M. Palacova ²; M. Navratilova ¹; R. Gaillyová ⁶; A. Puchmajerová ⁷; A. Křepelová ⁷; E. Macháčková ¹
Authors‘ workplace: Oddělení epidemiologie a genetiky nádorů, Masarykův onkologický ústav, Brno ¹; Klinika komplexní onkologické péče, Masarykův onkologický ústav, Brno ²; Oddělení radiologie, Masarykův onkologický ústav, Brno ³; Klinika dětské onkologie, Masarykův onkologický ústav, Brno ⁴; Klinika dětské radiologie, Masarykův onkologický ústav, Brno ⁵; Oddělení lékařské genetiky, Fakultní nemocnice Brno ⁶; Ústav biologie a lékařské genetiky, Masarykův onkologický ústav, Brno ⁷; Klinika zobrazovacích metod, Fakultní nemocnice v Motole, Praha ⁸
Published in: Klin Onkol 2012; 25(Supplementum): 49-54

Overview

Li-Fraumeni syndrome (LFS) is one of the most serious hereditary cancer syndromes with high risk of malignancy already in childhood. Adrenocortical carcinoma, brain tumor, leukemia, sarcoma are the most frequent malignancies in children. Early breast cancer, brain tumor, sarcoma, skin cancer, gastrointestinal, lung, gynecological, hematological and other malignancies can be seen in adults. Predictive testing in families with detected LFS and TP53 mutation is offered from the age of 18 for various reasons. One of the most important reasons is a very limited effectivity of prevention especially in children, also the possible risk of psychological harm to the child and his family caused by the diagnosis of this syndrome. Progress in diagnostic methods, especially total body MRI, enables to propose preventive care for early cancer diagnoses for children and adults. Biochemical tests, ultrasound, MRI may improve survival of these high risk individuals and support the possibility of predictive testing in children.

Key words:
TP53 gene – Li-Fraumeni syndrome – magnetic resonance imaging – MRI – prevention – tumors

This study was supported by grants of the European Regional Development Fund and grants of the Czech republic´s national budget.

The authors declare they have no potential conflicts of interest concerning drugs, products, or services used in the study.

The Editorial board declares that the manuscript met the ICMJE “uniform requirements” for biomedical papers.

Submitted:
27. 5. 2012

Accepted:
25. 6. 2012

Sources

1. Li FP, Fraumeni JF Jr. Soft-tissue sarcomas, breast cancer, and other neoplasms: a familial syndrome? Ann Intern Med 1969; 71(4): 747–752.

2. Li FP, Garber JE, Friend SH et al. Recommendations on predictive testing for germ line p53 mutations among cancer-prone individuals. J Natl Cancer Inst 1992; 84(15): 1156–1160.

3. Krutílková V, Trková M, Kodet R et al. Syndrom Li-Fraumeni. Čes Slov Pediat 2003; 58(8): 552–555.

4. Masciari S, Dewanwala A, Stoffel EM et al. Gastric cancer in individuals with Li-Fraumeni syndrome. Genet Med 2011; 13(7): 651–657.

5. Sedláček Z, Kodet R, Poustka A et al. A database of germline p53 mutations in cancer-prone families. Nucleic Acids Res 1998; 26(1): 214–215.

6. Ruijs MW, Broeks A, Menko FH et al. The contribution of CHEK2 to the TP53-negative Li-Fraumeni phenotype. Hered Cancer Clin Pract 2009; 7(1): 4.

7. Palmero EI, Achatz MI, Ashton-Prolla P et al. Tumor protein 53 mutations and inherited cancer: beyond Li--Fraumeni syndrome. Curr Opin Oncol 2010; 22(1): 64–69.

8. Trkova M, Prochazkova K, Krutilkova V et al. Telomere length in peripheral blood cells of germline TP53 mutation carriers is shorter than that of normal individuals of corresponding age. Cancer 2007; 110(3): 694–702.

9. Wu CC, Krahe R, Lozano G et al. Joint effects of germ-line TP53 mutation, MDM2 SNP309 and gender on cancer risk in family studies of Li-Fraumeni syndrome. Hum Genet 2011; 129(6): 663–673.

10. Marcel V, Palmero EI, Falagan-Lotsch P et al. TP53 PIN3 and MDM2 SNP309 polymorphisms as genetic modifiers in Li-Fraumeni syndrome: impact on age at first diagnosis. J Med Genet 2009; 46(11): 766–772.

11. Gonzales KD, Buzin CH, Noltner KA et al. High frequency of de novo mutations in Li-Fraumeni syndrome. J Med Genet 2009; 46(10): 686–693.

12. Krutílková V, Trková M, Fleitz J at al. Identification of five families strengthens the link between childhood choroid plexus carcinoma and germline TP53 mutation. Eur J Cancer 2005; 41(11): 1597–1603.

13. Plevová P, Krutílková V, Petráková K et al. Li-Fraumeni syndrom. Klin Onkol 2009; 22 (Suppl): S20–S22.

14. Tinat J, Bougeard G, Baert-Desurmont S et al. 2009 version of the Chompret criteria for Li-Fraumeni syndrome. J Clin Oncol 2009; 27(26): e108–e109.

15. Chompret A, Brugières L, Ronsin M et al. P53 germline mutations in childhood cancers and cancer risk for carrier individuals. Br J Cancer 2000; 82(12): 1932–1937.

16. Li FP, Fraumeni JF Jr, Mulvihill JJ et al. A cancer family syndrome in twenty-four kindreds. Cancer Res 1988; 48(18): 5358–5362.

17. Chompret A, Abel A, Stoppa-Lyonnet D et al. Sensitivity and predictive value of criteria for p53 germline mutation screening. J Med Genet 2001; 38(1): 43–47.

18. Hodgson SV, Foulkes WD, Eng C et al. A practical guide to human cancer genetics. Cambridge: University Press 2007.

19. Villani A, Tabori U, Schiffman J et al. Biochemical and imaging surveillance in germline TP53 mutation carriers with Li-Fraumeni syndrome: a prospective observational study. Lancet Oncol 2011; 12(6): 559–567.

20. Trková M, Sedláček Z. Kdy má smysl hledat v rodinách onkologických pacientů zárodečné mutace v genu TP53? Čas Lék Česk 2003; 142(4): 220–225.

21. Ruijs MW, Verhoef S, Rookus MA et al. TP53 mutation testing in 180 families suspected of Li-Fraumeni syndrome: mutation detection rate and relative frequency of cancers in different familial phenotypes. J Med Genet 2010; 47(6): 421–428.