Till startsida
Webbkarta
Till innehåll Läs mer om hur kakor används på gu.se

A new GTF2I-BRAF fusion mediating MAPK pathway activation in pilocytic astrocytoma

Artikel i vetenskaplig tidskrift
Författare Tajana Tesan Tomic
Josefin Olausson
Annica Wilzén
Magnus Sabel
Katarina Truvé
H. Sjogren
S. Dosa
Magnus Tisell
Birgitta Lannering
F. Enlund
Tommy Martinsson
Pierre Åman
Frida Abel
Publicerad i PLoS ONE
Volym 12
Nummer/häfte 4
ISSN 1932-6203
Publiceringsår 2017
Publicerad vid Institutionen för biomedicin, avdelningen för medicinsk genetik och klinisk genetik
Sahlgrenska Cancer Center
Institutionen för biomedicin
Core Facilities, Bioinformatics
Språk English
Länkar doi.org/10.1371/journal.pone.017563...
Ämnesord low-grade gliomas, central-nervous-system, braf gene, tumors, duplication, 7q34, classification, kiaa1549-braf, expression, resistance, Science & Technology - Other Topics
Ämneskategorier Klinisk medicin

Sammanfattning

Pilocytic astrocytoma (PA) is the most common pediatric brain tumor. A recurrent feature of PA is deregulation of the mitogen activated protein kinase (MAPK) pathway most often through KIAA1549-BRAF fusion, but also by other BRAF- or RAF1-gene fusions and point mutations (e.g. BRAFV600E). These features may serve as diagnostic and prognostic markers, and also facilitate development of targeted therapy. The aims of this study were to characterize the genetic alterations underlying the development of PA in six tumor cases, and evaluate methods for fusion oncogene detection. Using a combined analysis of RNA sequencing and copy number variation data we identified a new BRAF fusion involving the 5' gene fusion partner GTF2I (7q11.23), not previously described in PA. The new GTF2I-BRAF 19-10 fusion was found in one case, while the other five cases harbored the frequent KIAA1549-BRAF 16-9 fusion gene. Similar to other BRAF fusions, the GTF2I-BRAF fusion retains an intact BRAF kinase domain while the inhibitory N-terminal domain is lost. Functional studies on GTF2I-BRAF showed elevated MAPK pathway activation compared to BRAF WT. Comparing fusion detection methods, we found Fluorescence in situ hybridization with BRAF break apart probe as the most sensitive method for detection of different BRAF rearrangements (GTF2I-BRAF and KIAA1549-BRAF). Our finding of a new BRAF fusion in PA further emphasis the important role of B-Raf in tumorigenesis of these tumor types. Moreover, the consistency and growing list of BRAF/RAF gene fusions suggests these rearrangements to be informative tumor markers in molecular diagnostics, which could guide future treatment strategies.

Sidansvarig: Webbredaktion|Sidan uppdaterades: 2012-09-11
Dela:

På Göteborgs universitet använder vi kakor (cookies) för att webbplatsen ska fungera på ett bra sätt för dig. Genom att surfa vidare godkänner du att vi använder kakor.  Vad är kakor?