Skip to main content
Log in

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

  • Original Article
  • Published:
Brain Tumor Pathology Aims and scope Submit manuscript

Abstract

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.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  1. Mardis ER, Ding L, Dooling DJ et al (2009) Recurring mutations found by sequencing an acute myeloid leukemia genome. N Engl J Med 361:1058–1066

    Article  PubMed  CAS  Google Scholar 

  2. Ohgaki H, Kleihues P (2011) Genetic profile of astrocytic and oligodendroglial gliomas. Brain Tumor Pathol 28:177–183

    Article  PubMed  CAS  Google Scholar 

  3. Dang L, White DW, Gross S et al (2009) Cancer-associated IDH1 mutations produce 2-hydroxyglutarate. Nature 462:739–744

    Article  PubMed  CAS  Google Scholar 

  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 18:553–567

    Article  PubMed  CAS  Google Scholar 

  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 224:334–343

    Article  PubMed  CAS  Google Scholar 

  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–E2049

    Article  PubMed  CAS  Google Scholar 

  7. Pamir MN, Ozduman K (2006) Analysis of radiological features relative to histopathology in 42 skull-base chordomas and chondrosarcomas. Eur J Radiol 58:461–470

    Article  PubMed  Google Scholar 

  8. Almefty K, Pravdenkova S, Colli BO et al (2007) Chordoma and chondrosarcoma: similar, but quite different, skull base tumors. Cancer 110:2457–2467

    Article  PubMed  Google Scholar 

  9. Fletcher CDM, Krishnan Unni K, Mertens F (2002) WHO classification of tumours of the soft tissues and bones. IARC Press, Lyon

    Google Scholar 

  10. Ohgaki H, Dessen P, Jourde B et al (2008) Genetic pathways to glioblastoma: a population-based study. Cancer Res 64:6892–6899

    Article  Google Scholar 

  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 174:1149–1153

    Article  PubMed  CAS  Google Scholar 

  12. Capper D, Weissert S, Balss J et al (2010) Characterization of R132H mutation-specific IDH1 antibody binding in brain tumors. Brain Pathol 20:245–254

    Article  PubMed  CAS  Google Scholar 

  13. Yan H, Parsons DW, Jin G et al (2009) IDH1 and IDH2 mutations in gliomas. N Engl J Med 360:765–773

    Article  PubMed  CAS  Google Scholar 

  14. Thol F, Damm F, Wagner K et al (2010) Prognostic impact of IDH2 mutations in cytogenetically normal acute myeloid leukemia. Blood 116:614–616

    Article  PubMed  CAS  Google Scholar 

  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 21:1461–1469

    Article  PubMed  CAS  Google Scholar 

  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 406:608–613

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

We thank the following doctors for providing the chondrosarcoma and chordoma samples: Dr. Motohiro Kojima (Division of Diagnostic Pathology, Showa University Hospital: case 8), Dr. Hideyuki Onuma (Department of Pathology, Matsue Red Cross Hospital: case 9), and Dr. Raita Fukaya (Department of Neurosurgery, Shizuoka City Shimizu hospital: case 23). This work was supported in part by a research grant from Gunma Medical Association.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Hayato Ikota.

Additional information

M. Arai and S. Nobusawa contributed equally to this work.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Arai, M., Nobusawa, S., Ikota, H. et al. Frequent IDH1/2 mutations in intracranial chondrosarcoma: a possible diagnostic clue for its differentiation from chordoma. Brain Tumor Pathol 29, 201–206 (2012). https://doi.org/10.1007/s10014-012-0085-1

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10014-012-0085-1

Keywords

Navigation