BRAF mutation status in gastrointestinal stromal tumors.
Gastrointestinal stromal tumors (GISTs) are mesenchymal tumors characterized by mutations of KIT or PDGFRA. The objectives of this study were to evaluate BRAF mutations in GISTs and then to correlate BRAF mutational status in the tumor with clinical parameters, with B-raf expression, and with activation of some cellular pathways. BRAF mutation was screened in 321 GISTs with 70 wild-type GISTs. BRAF V600E was detected in 9 (13%) of 70 wild-type GISTs. No mutations were detected in GISTs bearing KIT or PDGFRA mutations. BRAF V600E detection in the tumor does not induce a higher expression of the B-raf protein or the preferential activation of the p42/44 mitogen-activated protein kinase (MAPK) signaling pathway compared with GISTs without the BRAF mutation. In comparison with the GIST group with KIT or PDGFRA mutation or the wild-type GIST group without BRAF mutation, the wild-type GIST group with a BRAF mutation is not different in terms of B-raf expression or the p44/42 MAPK- or AKT-activated signaling pathway.
Hostein
Isabelle
I
1Department of Pathology, Institut Bergonié, Bordeaux, France.
Faur
Nicolas
N
Primois
Charlotte
C
Boury
Frédérique
F
Denard
Jérome
J
Emile
Jean-François
JF
Bringuier
Pierre-Paul
PP
Scoazec
Jean-Yves
JY
Coindre
Jean-Michel
JM
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000378:metabolism; D015153:Blotting, Western; D002648:Child; D002851:Chromatography, High Pressure Liquid; D004252:DNA Mutational Analysis; D004273:DNA, Neoplasm / Q000032:analysis; D005260:Female; D046152:Gastrointestinal Stromal Tumors / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007124:Immunoenzyme Techniques; D008297:Male; D008875:Middle Aged; D019950:Mitogen-Activated Protein Kinase 1 / Q000096:biosynthesis / Q000235:genetics; D009154:Mutation; D009691:Nucleic Acid Denaturation; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics* / Q000378:metabolism; D015398:Signal Transduction; D055815:Young Adult
D014408:Biomarkers, Tumor; D004273:DNA, Neoplasm; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf; D019950:Mitogen-Activated Protein Kinase 1