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: 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
• Journal: Brain pathology (Zurich, Switzerland) (Brain Pathol) Vol. 22 Issue 6 Pg. 834-40 (Nov 2012) ISSN: 1750-3639 [Electronic] Switzerland
• PMID: 22568401 (Publication Type: Journal Article)
• Copyright: © 2012 The Authors; Brain Pathology © 2012 International Society of Neuropathology.

Chemical References

• BRAF-KIAA1549 fusion protein, human
• Oncogene Proteins, Fusion
• BRAF protein, human
• Proto-Oncogene Proteins B-raf

Topics

• Brain Neoplasms (genetics, pathology)
• Chromosomes, Human, Pair 1 (genetics)
• Chromosomes, Human, Pair 19 (genetics)
• Glioma (genetics, pathology)
• Humans
• In Situ Hybridization, Fluorescence
• Mutation
• Neoplasm Grading
• Oncogene Proteins, Fusion (genetics)
• Proto-Oncogene Proteins B-raf (genetics)
• Reverse Transcriptase Polymerase Chain Reaction