Brain Tumor Pathology

, Volume 29, Issue 4, pp 201–206

Frequent IDH1/2 mutations in intracranial chondrosarcoma: a possible diagnostic clue for its differentiation from chordoma

  • Motohiro Arai
  • Sumihito Nobusawa
  • Hayato Ikota
  • Sunao Takemura
  • Yoichi Nakazato
Original Article


Mutations in the genes encoding isocitrate dehydrogenase (IDH) 1/2 have been detected in a significant proportion of diffuse gliomas and in a small fraction of acute myeloid leukemia (AML) cases. Recently, in an examination of various types of mesenchymal tumor, IDH1/2 mutations were only found in cartilaginous tumors including central conventional and periosteal enchondromas/chondrosarcomas. The frequency of IDH1/2 mutations was 56%, and the IDH1 R132C mutation, which is not common in diffuse gliomas or AML, accounted for 40% of these mutations. In this study, we investigated the IDH1/2 mutation status of intracranial chondrosarcomas and chordomas, which are morphologically similar and affect similar regions of the cranial cavity. Of the 13 chondrosarcomas analyzed, six (46.1%) displayed IDH1/2 mutations (the predominant type was IDH1 R132C). Also, an IDH2 mutation (R172S) was observed in one case. Conversely, none of the ten chordomas analyzed displayed any IDH1 or IDH2 mutations. Our data suggest that the IDH1/2 mutation status could be valuable for distinguishing intracranial chondrosarcomas from chordomas.


Isocitrate dehydrogenase Mutation Chondrosarcoma Chordoma 


  1. 1.
    Mardis ER, Ding L, Dooling DJ et al (2009) Recurring mutations found by sequencing an acute myeloid leukemia genome. N Engl J Med 361:1058–1066PubMedCrossRefGoogle Scholar
  2. 2.
    Ohgaki H, Kleihues P (2011) Genetic profile of astrocytic and oligodendroglial gliomas. Brain Tumor Pathol 28:177–183PubMedCrossRefGoogle Scholar
  3. 3.
    Dang L, White DW, Gross S et al (2009) Cancer-associated IDH1 mutations produce 2-hydroxyglutarate. Nature 462:739–744PubMedCrossRefGoogle Scholar
  4. 4.
    Figueroa ME, Abdel-Wahab O, Lu C et al (2010) Leukemic IDH1 and IDH2 mutations result in a hypermethylation phenotype, disrupt TET2 function, and impair hematopoietic differentiation. Cancer Cell 18:553–567PubMedCrossRefGoogle Scholar
  5. 5.
    Amary MF, Bacsi K, Maggiani F et al (2011) IDH1 and IDH2 mutations are frequent events in central chondrosarcoma and central and periosteal chondromas but not in other mesenchymal tumours. J Pathol 224:334–343PubMedCrossRefGoogle Scholar
  6. 6.
    Szuhai K, Jennes I, de Jong D et al (2011) Tiling resolution array-CGH shows that somatic mosaic deletion of the EXT gene is causative in EXT gene mutation negative multiple osteochondromas patients. Hum Mutat 32:E2036–E2049PubMedCrossRefGoogle Scholar
  7. 7.
    Pamir MN, Ozduman K (2006) Analysis of radiological features relative to histopathology in 42 skull-base chordomas and chondrosarcomas. Eur J Radiol 58:461–470PubMedCrossRefGoogle Scholar
  8. 8.
    Almefty K, Pravdenkova S, Colli BO et al (2007) Chordoma and chondrosarcoma: similar, but quite different, skull base tumors. Cancer 110:2457–2467PubMedCrossRefGoogle Scholar
  9. 9.
    Fletcher CDM, Krishnan Unni K, Mertens F (2002) WHO classification of tumours of the soft tissues and bones. IARC Press, LyonGoogle Scholar
  10. 10.
    Ohgaki H, Dessen P, Jourde B et al (2008) Genetic pathways to glioblastoma: a population-based study. Cancer Res 64:6892–6899CrossRefGoogle Scholar
  11. 11.
    Watanabe T, Nobusawa S, Kleihues P et al (2009) IDH1 mutations are early events in the development of astrocytomas and oligodendrogliomas. Am J Pathol 174:1149–1153PubMedCrossRefGoogle Scholar
  12. 12.
    Capper D, Weissert S, Balss J et al (2010) Characterization of R132H mutation-specific IDH1 antibody binding in brain tumors. Brain Pathol 20:245–254PubMedCrossRefGoogle Scholar
  13. 13.
    Yan H, Parsons DW, Jin G et al (2009) IDH1 and IDH2 mutations in gliomas. N Engl J Med 360:765–773PubMedCrossRefGoogle Scholar
  14. 14.
    Thol F, Damm F, Wagner K et al (2010) Prognostic impact of IDH2 mutations in cytogenetically normal acute myeloid leukemia. Blood 116:614–616PubMedCrossRefGoogle Scholar
  15. 15.
    Oakley GJ, Fuhrer K, Seethala RR (2008) Brachyury, SOX-9, and podoplanin, new markers in the skull base chordoma vs chondrosarcoma differential: a tissue microarray-based comparative analysis. Mod Pathol 21:1461–1469PubMedCrossRefGoogle Scholar
  16. 16.
    Kaneko MK, Tian W, Takano S et al (2011) Establishment of a novel monoclonal antibody SMab-1 specific for IDH1-R132S mutation. Biochem Biophys Res Commun 406:608–613PubMedCrossRefGoogle Scholar

Copyright information

© The Japan Society of Brain Tumor Pathology 2012

Authors and Affiliations

  • Motohiro Arai
    • 1
  • Sumihito Nobusawa
    • 1
  • Hayato Ikota
    • 1
  • Sunao Takemura
    • 2
  • Yoichi Nakazato
    • 1
  1. 1.Department of Human PathologyGunma University Graduate School of MedicineMaebashiJapan
  2. 2.Department of NeurosurgeryYamagata University Faculty of MedicineYamagataJapan

Personalised recommendations