Frequent BRAF gain in low-grade diffuse gliomas with 1p/19q loss.

Young Ho Kim, Naosuke Nonoguchi, Werner Paulus, Benjamin Brokinkel, Kathy Keyvani, Ulrich Sure, Karsten Wrede, Luigi Mariani, Felice Giangaspero, Yuko Tanaka, Yoichi Nakazato, Anne Vital, Michel Mittelbronn, Arie Perry, Hiroko Ohgaki

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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 BRAF(V600E) mutation was also detected in one oligodendroglioma, and a BRAF(A598V) 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.

Original languageEnglish
Pages (from-to)834-840
Number of pages7
JournalBrain Pathology
Volume22
Issue number6
Publication statusPublished - Nov 2012

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ASJC Scopus subject areas

  • Medicine(all)

Cite this

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., & Ohgaki, H. (2012). Frequent BRAF gain in low-grade diffuse gliomas with 1p/19q loss. Brain Pathology, 22(6), 834-840.