title: KIAA1549-BRAF fusions and IDH mutations can coexist in diffuse gliomas of adults.
abstract: KIAA1549-BRAF fusion gene and isocitrate dehydrogenase (IDH) mutations are considered two mutually exclusive genetic events in pilocytic astrocytomas and diffuse gliomas, respectively. We investigated the presence of the KIAA1549-BRAF fusion gene in conjunction with IDH mutations and 1p/19q loss in 185 adult diffuse gliomas. Moreover BRAF(v600E)  mutation was also screened. The KIAA1549-BRAF fusion gene was evaluated by reverse-transcription polymerase chain reaction (RT-PCR) and sequencing. We found IDH mutations in 125 out 175 cases (71.4%). There were KIAA1549-BRAF fusion gene in 17 out of 180 (9.4%) cases and BRAF(v600E)  in 2 out of 133 (1.5%) cases. In 11 of these 17 cases, both IDH mutations and the KIAA1549-BRAF fusion were present, as independent molecular events. Moreover, 6 of 17 cases showed co-presence of 1p/19q loss, IDH mutations and KIAA1549-BRAF fusion. Among the 17 cases with KIAA1549-BRAF fusion gene 15 (88.2%) were oligodendroglial neoplasms. Similarly, the two cases with BRAF(v600E)  mutation were both oligodendroglioma and one had IDH mutations and 1p/19q co-deletion. Our results suggest that in a small fraction of diffuse gliomas, KIAA1549-BRAF fusion gene and BRAF(v600E)  mutation may be responsible for deregulation of the Ras-RAF-ERK signaling pathway. Such alterations are more frequent in oligodendroglial neoplasm and may be co-present with IDH mutations and 1p/19q loss.
authors.affiliation: Bone Marrow Transplant Unit, Microcitemico Hospital, Cagliari, Italy.
authors.forename: Manuela
authors.initials: M
authors.lastname: Badiali
authors.forename: Vincent
authors.initials: V
authors.lastname: Gleize
authors.forename: Sophie
authors.initials: S
authors.lastname: Paris
authors.forename: Loredana
authors.initials: L
authors.lastname: Moi
authors.forename: Selma
authors.initials: S
authors.lastname: Elhouadani
authors.forename: Antonietta
authors.initials: A
authors.lastname: Arcella
authors.forename: Roberta
authors.initials: R
authors.lastname: Morace
authors.forename: Manila
authors.initials: M
authors.lastname: Antonelli
authors.forename: Francesca Romana
authors.initials: FR
authors.lastname: Buttarelli
authors.forename: Dominique
authors.initials: D
authors.lastname: Figarella-Branger
authors.forename: Young-Ho
authors.initials: YH
authors.lastname: Kim
authors.forename: Hiroko
authors.initials: H
authors.lastname: Ohgaki
authors.forename: Karima
authors.initials: K
authors.lastname: Mokhtari
authors.forename: Marc
authors.initials: M
authors.lastname: Sanson
authors.forename: Felice
authors.initials: F
authors.lastname: Giangaspero
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001932:Brain Neoplasms / Q000235:genetics*; D005260:Female; D005910:Glioma / Q000235:genetics*; D006801:Humans; D007521:Isocitrate Dehydrogenase / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D015514:Oncogene Proteins, Fusion / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D055815:Young Adult
chemical_list: C568616:BRAF-KIAA1549 fusion protein, human; D015514:Oncogene Proteins, Fusion; D007521:Isocitrate Dehydrogenase