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

Research output: Contribution to journalArticle

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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Oligodendroglioma
Glioma
Astrocytoma
Mutation
Chromosome Duplication
Fluorescence In Situ Hybridization
Complementary DNA
Logistic Models
Regression Analysis
Polymerase Chain Reaction

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Kim, Y. H., Nonoguchi, N., Paulus, W., Brokinkel, B., Keyvani, K., Sure, U., ... Ohgaki, H. (2012). Frequent BRAF gain in low-grade diffuse gliomas with 1p/19q loss. Brain Pathology, 22(6), 834-840.

Frequent BRAF gain in low-grade diffuse gliomas with 1p/19q loss. / Kim, Young Ho; Nonoguchi, Naosuke; Paulus, Werner; Brokinkel, Benjamin; Keyvani, Kathy; Sure, Ulrich; Wrede, Karsten; Mariani, Luigi; Giangaspero, Felice; Tanaka, Yuko; Nakazato, Yoichi; Vital, Anne; Mittelbronn, Michel; Perry, Arie; Ohgaki, Hiroko.

In: Brain Pathology, Vol. 22, No. 6, 11.2012, p. 834-840.

Research output: Contribution to journalArticle

Kim, YH, 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, vol. 22, no. 6, pp. 834-840.
Kim YH, Nonoguchi N, Paulus W, Brokinkel B, Keyvani K, Sure U et al. Frequent BRAF gain in low-grade diffuse gliomas with 1p/19q loss. Brain Pathology. 2012 Nov;22(6):834-840.
Kim, Young Ho ; Nonoguchi, Naosuke ; Paulus, Werner ; Brokinkel, Benjamin ; Keyvani, Kathy ; Sure, Ulrich ; Wrede, Karsten ; Mariani, Luigi ; Giangaspero, Felice ; Tanaka, Yuko ; Nakazato, Yoichi ; Vital, Anne ; Mittelbronn, Michel ; Perry, Arie ; Ohgaki, Hiroko. / Frequent BRAF gain in low-grade diffuse gliomas with 1p/19q loss. In: Brain Pathology. 2012 ; Vol. 22, No. 6. pp. 834-840.
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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.",
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AU - Keyvani, Kathy

AU - Sure, Ulrich

AU - Wrede, Karsten

AU - Mariani, Luigi

AU - Giangaspero, Felice

AU - Tanaka, Yuko

AU - Nakazato, Yoichi

AU - Vital, Anne

AU - Mittelbronn, Michel

AU - Perry, Arie

AU - Ohgaki, Hiroko

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AB - 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.

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