Acta Neuropathologica

, Volume 117, Issue 6, pp 653–656 | Cite as

Selective acquisition of IDH1 R132C mutations in astrocytomas associated with Li-Fraumeni syndrome

  • Takuya Watanabe
  • Anne Vital
  • Sumihito Nobusawa
  • Paul Kleihues
  • Hiroko Ohgaki
Original Paper

Abstract

Mutations of the IDH1 gene are frequent in gliomas, with R132H (CGT → CAT) being the most common (>85%). In astrocytomas, IDH1 mutations are typically co-present with, or precede, TP53 mutations. We assessed IDH1 mutations in brain tumors diagnosed in patients from three families with Li-Fraumeni syndrome. We identified IDH1 mutations in five astrocytomas that developed in carriers of a TP53 germline mutation. Without exception, all were R132C (CGT → TGT), which in sporadic astrocytomas accounts for <5% of IDH1 mutations. This remarkably selective occurrence of R132C mutations may reflect differences in the sequence of genetic events, with a preference for R132C mutations in astrocytes or precursor cells that already carry a germline TP53 mutation.

Keywords

Li-Fraumeni syndrome IDH1 mutation Astrocytoma TP53 germline mutation 

References

  1. 1.
    Balss J, Meyer J, Mueller W, Korshunov A, Hartmann C, von Deimling A (2008) Analysis of the IDH1 codon 132 mutation in brain tumors. Acta Neuropathol 116:597–602PubMedCrossRefGoogle Scholar
  2. 2.
    Bleeker FE, Lamba S, Leenstra S, Troost D, Hulsebos T, Vandertop WP, Frattini M, Molinari F, Knowles M, Cerrato A, Rodolfo M, Scarpa A, Felicioni L, Buttitta F, Malatesta S, Marchetti A, Bardelli A (2009) IDH1 mutations at residue p.R132 (IDH1(R132)) occur frequently in high-grade gliomas but not in other solid tumors. Hum Mutat 30:7–11PubMedCrossRefGoogle Scholar
  3. 3.
    Devlin TM (2006) Textbook of biochemistry with clinical correlations. Wiley-Liss, WilmingtonGoogle Scholar
  4. 4.
    Kleihues P, Schauble B, zur Hausen A, Esteve J, Ohgaki H (1997) Tumours associated with p53 germline mutations. Am J Pathol 150:1–13PubMedGoogle Scholar
  5. 5.
    Louis DN, Ohgaki H, Wiestler OD, Cavenee WK (2007) WHO classification of tumours of the central nervous system. IARC, LyonGoogle Scholar
  6. 6.
    Lubbe J, von Ammon K, Watanabe K, Hegi ME, Kleihues P (1995) Familial brain tumor syndrome associated with a p53 germline deletion of codon 236. Brain Pathol 5:15–23PubMedCrossRefGoogle Scholar
  7. 7.
    Narahara K, Kimura S, Kikkawa K, Takahashi Y, Wakita Y, Kasai R, Nagai S, Nishibayashi Y, Kimoto H (1985) Probable assignment of soluble isocitrate dehydrogenase (IDH1) to 2q33.3. Hum Genet 71:37–40PubMedCrossRefGoogle Scholar
  8. 8.
    Ohgaki H, Dessen P, Jourde B, Horstmann S, Nishikawa T, Di Patre PL, Burkhard C, Schuler D, Probst-Hensch NM, Maiorka PC, Baeza N, Pisani P, Yonekawa Y, Yasargil MG, Lutolf UM, Kleihues P (2004) Genetic pathways to glioblastoma: a population-based study. Cancer Res 64:6892–6899PubMedCrossRefGoogle Scholar
  9. 9.
    Olivier M, Goldger DE, Sodha N, Ohgaki H, Kleihues P, Hainaut P, Eeles RA (2003) Li-Fraumeni and related syndromes: correlation between tumor type, family structure and TP53 genotype. Cancer Res 63:6643–6650PubMedGoogle Scholar
  10. 10.
    Parsons DW, Jones S, Zhang X, Lin JC-H, Leary RJ, Angenendt P, Mankoo P, Carter H, Siu IM, Gallia GL, Olivi A, McLendon R, Rasheed BA, Keir S, Nikolskaya T, Nikolsky Y, Busam DA, Tekleab H, Diaz LA Jr, Hartigan J, Smith DR, Strausberg RL, Marie SKN, Shinjo SMO, Yan H, Riggins GJ, Bigner DD, Karchin R, Papadopoulos N, Parmigiani G, Vogelstein B, Velculescu VE, Kinzler KW (2008) An integrated genomic analysis of human glioblastoma multiforme. Science 321:1807–1812PubMedCrossRefGoogle Scholar
  11. 11.
    Vital A, Bringuier PP, Huang H, San Galli F, Rivel J, Ansoborlo S, Cazauran JM, Taillandier L, Kleihues P, Ohgaki H (1998) Astrocytomas and choroid plexus tumors in two families with identical p53 germline mutations. J Neuropathol Exp Neurol 57:1061–1069PubMedCrossRefGoogle Scholar
  12. 12.
    Watanabe T, Nobusawa S, Kleihues P, Ohgaki H (2009) IDH1 mutations are early events in the development of astrocytomas and oligodendrogliomas. Am J Pathol 174:1149–1153Google Scholar
  13. 13.
    Yan H, Parsons DW, Jin G, McLendon R, Rasheed BA, Yuan W, Kos I, Batinic-Haberle I, Jones S, Riggins GJ, Friedman H, Friedman A, Reardon D, Herndon J, Kinzler KW, Velculescu VE, Vogelstein B, Bigner DD (2009) IDH1 and IDH2 mutations in gliomas. N Engl J Med 360:765–773PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag 2009

Authors and Affiliations

  • Takuya Watanabe
    • 1
  • Anne Vital
    • 2
  • Sumihito Nobusawa
    • 1
  • Paul Kleihues
    • 3
  • Hiroko Ohgaki
    • 1
  1. 1.Pathology GroupInternational Agency for Research on CancerLyonFrance
  2. 2.Bordeaux Institute of NeuroscienceBordeauxFrance
  3. 3.Department of PathologyUniversity Hospital ZurichZurichSwitzerland

Personalised recommendations