Acta Neuropathologica

, Volume 120, Issue 2, pp 253–260

Focal genomic amplification at 19q13.42 comprises a powerful diagnostic marker for embryonal tumors with ependymoblastic rosettes

  • Andrey Korshunov
  • Marc Remke
  • Marco Gessi
  • Marina Ryzhova
  • Thomas Hielscher
  • Hendrik Witt
  • Vivienne Tobias
  • Anna Maria Buccoliero
  • Iacopo Sardi
  • Marina Paola Gardiman
  • Jose Bonnin
  • Bernd Scheithauer
  • Andreas E. Kulozik
  • Olaf Witt
  • Sverre Mork
  • Andreas von Deimling
  • Otmar D. Wiestler
  • Felice Giangaspero
  • Marc Rosenblum
  • Torsten Pietsch
  • Peter Lichter
  • Stefan M. Pfister
Original Paper

DOI: 10.1007/s00401-010-0688-8

Cite this article as:
Korshunov, A., Remke, M., Gessi, M. et al. Acta Neuropathol (2010) 120: 253. doi:10.1007/s00401-010-0688-8

Abstract

Ependymoblastoma (EBL) and embryonal tumor with abundant neuropil and true rosettes (ETANTR) are very aggressive embryonal neoplasms characterized by the presence of ependymoblastic multilayered rosettes typically occurring in children below 6 years of age. It has not been established whether these two tumors really comprise distinct entities. Earlier, using array-CGH, we identified a unique focal amplification at 19q13.42 in a case of ETANTR. In the present study, we investigated this locus by fluorescence in situ hybridization in 41 tumors, which had morphologically been diagnosed as EBL or ETANTR. Strikingly, FISH analysis revealed 19q13.42 amplifications in 37/40 samples (93%). Among tumors harboring the amplification, 19 samples were identified as ETANTR and 18 as EBL. The three remaining tumors showed a polysomy of chromosome 19. Analysis of recurrent/metastatic tumors (n = 7) showed that the proportion of nuclei carrying the amplification was increased (up to 80–100% of nuclei) in comparison to the corresponding primary tumors. In conclusion, we have identified a hallmark cytogenetic aberration occurring in virtually all embryonal brain tumors with ependymoblastic rosettes suggesting that ETANTR and EBL comprise a single biological entity. FISH analysis of the 19q13.42 locus is a very promising diagnostic tool to identify a subset of primitive neuroectodermal tumors with distinct morphology, biology, and clinical behavior.

Keywords

Embryonal brain tumorETANTREpendymoblastoma19q13Molecular diagnosisWHO classification of CNS tumors

Copyright information

© Springer-Verlag 2010

Authors and Affiliations

  • Andrey Korshunov
    • 1
    • 2
  • Marc Remke
    • 3
    • 4
  • Marco Gessi
    • 5
  • Marina Ryzhova
    • 6
  • Thomas Hielscher
    • 7
  • Hendrik Witt
    • 3
    • 4
  • Vivienne Tobias
    • 8
  • Anna Maria Buccoliero
    • 9
  • Iacopo Sardi
    • 10
  • Marina Paola Gardiman
    • 11
  • Jose Bonnin
    • 12
  • Bernd Scheithauer
    • 13
  • Andreas E. Kulozik
    • 4
  • Olaf Witt
    • 4
    • 14
  • Sverre Mork
    • 15
  • Andreas von Deimling
    • 1
    • 2
  • Otmar D. Wiestler
    • 16
  • Felice Giangaspero
    • 17
    • 18
  • Marc Rosenblum
    • 19
  • Torsten Pietsch
    • 5
  • Peter Lichter
    • 3
  • Stefan M. Pfister
    • 3
    • 4
  1. 1.Clinical Cooperation Unit NeuropathologyGerman Cancer Research CenterHeidelbergGermany
  2. 2.Department of NeuropathologyUniversity of HeidelbergHeidelbergGermany
  3. 3.Division Molecular GeneticsGerman Cancer Research CenterHeidelbergGermany
  4. 4.Department of Pediatric Oncology, Hematology and ImmunologyUniversity of HeidelbergHeidelbergGermany
  5. 5.Department of NeuropathologyUniversity of BonnBonnGermany
  6. 6.NN Burdenko Neurosurgical InstituteMoscowRussia
  7. 7.Division of BiostatisticsGerman Cancer Research Center (DKFZ)HeidelbergGermany
  8. 8.Department of PathologySouth Eastern Area Laboratory Service (SEALS) at Sydney Children’s HospitalSydneyAustralia
  9. 9.Department of PathologyCareggi HospitalFlorenceItaly
  10. 10.Department of Pediatric Hematology-OncologyA.O.U. Meyer Children’s HospitalFlorenceItaly
  11. 11.Pathology UnitAzienda OspedalieraPaduaItaly
  12. 12.Division of NeuropathologyIndiana University School of MedicineIndianapolisUSA
  13. 13.Department of PathologyMayo ClinicRochesterUSA
  14. 14.Clinical Cooperation Unit Pediatric OncologyGerman Cancer Research CenterHeidelbergGermany
  15. 15.Department of PathologyThe Gades InstituteBergenNorway
  16. 16.German Cancer Research Center (DKFZ)HeidelbergGermany
  17. 17.Department of Experimental MedicineSapienza UniversityRomeItaly
  18. 18.IRCCS NeuromedPozzilli (IS)Italy
  19. 19.Department of PathologyMemorial Sloan-Kettering Cancer CenterNew YorkUSA