title: Frequent BRAF gain in low-grade diffuse gliomas with 1p/19q loss.
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.
authors.affiliation: International Agency for Research on Cancer, Lyon, France.
authors.forename: Young-Ho
authors.initials: YH
authors.lastname: Kim
authors.forename: Naosuke
authors.initials: N
authors.lastname: Nonoguchi
authors.forename: Werner
authors.initials: W
authors.lastname: Paulus
authors.forename: Benjamin
authors.initials: B
authors.lastname: Brokinkel
authors.forename: Kathy
authors.initials: K
authors.lastname: Keyvani
authors.forename: Ulrich
authors.initials: U
authors.lastname: Sure
authors.forename: Karsten
authors.initials: K
authors.lastname: Wrede
authors.forename: Luigi
authors.initials: L
authors.lastname: Mariani
authors.forename: Felice
authors.initials: F
authors.lastname: Giangaspero
authors.forename: Yuko
authors.initials: Y
authors.lastname: Tanaka
authors.forename: Yoichi
authors.initials: Y
authors.lastname: Nakazato
authors.forename: Anne
authors.initials: A
authors.lastname: Vital
authors.forename: Michel
authors.initials: M
authors.lastname: Mittelbronn
authors.forename: Arie
authors.initials: A
authors.lastname: Perry
authors.forename: Hiroko
authors.initials: H
authors.lastname: Ohgaki
mesh_terms: D001932:Brain Neoplasms / Q000235:genetics* / Q000473:pathology; D002878:Chromosomes, Human, Pair 1 / Q000235:genetics; D002888:Chromosomes, Human, Pair 19 / Q000235:genetics; D005910:Glioma / Q000235:genetics* / Q000473:pathology; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D009154:Mutation; D060787:Neoplasm Grading; D015514:Oncogene Proteins, Fusion / Q000235:genetics; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: C568616:BRAF-KIAA1549 fusion protein, human; D015514:Oncogene Proteins, Fusion; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf