RESEARCH ARTICLE

Frequent BRAF Gain in Low-Grade Diffuse Gliomas with 1p/19q Loss

  1. Young-Ho Kim1,
  2. Naosuke Nonoguchi1,
  3. Werner Paulus2,
  4. Benjamin Brokinkel3,
  5. Kathy Keyvani4,
  6. Ulrich Sure5,
  7. Karsten Wrede5,
  8. Luigi Mariani6,7,
  9. Felice Giangaspero8,9,
  10. Yuko Tanaka10,
  11. Yoichi Nakazato10,
  12. Anne Vital11,
  13. Michel Mittelbronn12,
  14. Arie Perry13,
  15. Hiroko Ohgaki1,*

Article first published online: 1 JUN 2012

DOI: 10.1111/j.1750-3639.2012.00601.x

Issue

Brain Pathology

Brain Pathology

Volume 22, Issue 6, pages 834–840, November 2012

Additional Information

How to Cite

Kim, Y.-H., Nonoguchi, N., Paulus, W., Brokinkel, B., Keyvani, K., Sure, U., Wrede, K., Mariani, L., Giangaspero, F., Tanaka, Y., Nakazato, Y., Vital, A., Mittelbronn, M., Perry, A. and Ohgaki, H. (2012), Frequent BRAF Gain in Low-Grade Diffuse Gliomas with 1p/19q Loss. Brain Pathology, 22: 834–840. doi: 10.1111/j.1750-3639.2012.00601.x

Author Information

  1. 1

    International Agency for Research on Cancer, Lyon, France

  2. 2

    Institute of Neuropathology

  3. 3

    Department of Neurosurgery, University Hospital Munster, Munster, Germany

  4. 4

    Institute of Pathology and Neuropathology

  5. 5

    Department of Neurosurgery, University Hospital Essen, Essen, Germany

  6. 6

    Department of Biomedicine, University Hospital, Basel, Switzerland

  7. 7

    Department of Biomedicine, University Hospital, Bern, Switzerland

  8. 8

    Department of Radiological, Oncological and Anatomo-Pathological Sciences, University Sapienza, Rome, Italy

  9. 9

    IRCCS Neuromed, Pozzilli, Italy

  10. 10

    Department of Pathology, Gunma University, Gunma, Japan

  11. 11

    Bordeaux Institute of Neuroscience, Bordeaux, France

  12. 12

    Edinger Institute (Neurological Institute), Goethe University Hospital, Frankfurt am Main, Germany

  13. 13

    Department of Pathology, Division of Neuropathology, University of California, San Francisco (UCSF), San Francisco, CA

*Hiroko Ohgaki, PhD, Section of Molecular Pathology, International Agency for Research on Cancer (IARC), 150 Cours Albert Thomas, 69372 Lyon Cedex 08, France (E-mail: ohgaki@iarc.fr)

Publication History

  1. Issue published online: 11 OCT 2012
  2. Article first published online: 1 JUN 2012
  3. Accepted manuscript online: 9 MAY 2012 03:37AM EST
  4. Received 8 March 2012; Accepted 30 April 2012; Published Online Article Accepted 9 May 2012

SEARCH

SEARCH BY CITATION

ARTICLE TOOLS

View Full Article (HTML) Get PDF (630K)

Keywords:

  • BRAF gain;
  • BRAF-KIAA1549 fusion gene;
  • BRAFV600E mutation;
  • diffuse astrocytoma;
  • oligodendroglioma

Abstract

Chromosomal 7q34 duplication and BRAF-KIAA1549 fusion is a characteristic genetic alteration in pilocytic astrocytomas. 7q34 gain appears to be common in diffuse astrocytomas, but its significance is unclear. We assessed BRAF gain and BRAF mutations in 123 low-grade diffuse gliomas, including 55 diffuse astrocytomas, 18 oligoastrocytomas and 50 oligodendrogliomas. Quantitative polymerase chain reaction (PCR) revealed BRAF gain in 17/50 (34%) oligodendrogliomas, a significantly higher frequency than in diffuse astrocytomas (7/55; 13%; P = 0.0112). BRAF gain was common in low-grade diffuse gliomas with 1p/19q loss (39%) and those lacking any of the genetic alterations analyzed (31%), but was rare in those with TP53 mutations (2%). Logistic regression analysis showed a significant positive association between 1p/19q loss and BRAF gain (P = 0.0032) and a significant negative association between TP53 mutations and BRAF gain (P = 0.0042). Fluorescence in situ hybridization (FISH) analysis of 26 low-grade diffuse gliomas with BRAF gain additionally revealed BRAF-KIAA1549 fusion in one oligodendroglioma. Sequencing of cDNA in 17 low-grade diffuse gliomas showed BRAF-KIAA1549 fusion in another oligodendroglioma. A BRAFV600E mutation was also detected in one oligodendroglioma, and a BRAFA598V in one diffuse astrocytoma. These results suggest that low-grade diffuse gliomas with 1p/19q loss have frequent BRAF gains, and a small fraction of oligodendrogliomas may show BRAF-KIAA1549 fusion.

View Full Article (HTML) Get PDF (630K)