Back to Search
Start Over
BRAF V600E mutation mediates FDG-methionine uptake mismatch in polymorphous low-grade neuroepithelial tumor of the young.
- Source :
-
Acta neuropathologica communications [Acta Neuropathol Commun] 2020 Aug 18; Vol. 8 (1), pp. 139. Date of Electronic Publication: 2020 Aug 18. - Publication Year :
- 2020
-
Abstract
- We present a case of a 14-year old boy with tumor-associated refractory epilepsy. Positron emission tomography imaging demonstrated a region with heterogeneous high <superscript>11</superscript> C-methionine uptake and a region with homogenous low <superscript>18</superscript> F-fluorodeoxyglucose uptake within the tumor. Histopathological and genomic analyses confirmed the tumor as BRAF V600E-mutated polymorphous low-grade neuroepithelial tumor of the young (PLNTY). Within the high-methionine-uptake region, we observed increased protein levels of L-type amino acid transporter 1 (LAT1), a major transporter of methionine; c-Myc; and constituents of the mitogen-activated protein kinase (MAPK) pathway. We also found that LAT1 expression was linked to the BRAF V600E mutation and subsequent activation of MAPK signaling and c-Myc. Pharmacological and genetic inhibition of the MAPK pathway suppressed c-Myc and LAT1 expression in BRAF V600E-mutated PLNTY and glioblastoma cells. The BRAF inhibitor dabrafenib moderately suppressed cell viability in PLNTY. Collectively, our results indicate that BRAF V600E mutation-activated MAPK signaling and downstream c-Myc induces specific metabolic alterations in PLNTY, and may represent an attractive target in the treatment of the disease.
- Subjects :
- Adolescent
Carbon Radioisotopes
Epilepsy, Temporal Lobe etiology
Fluorodeoxyglucose F18
Humans
Male
Methionine
Mutation
Positron-Emission Tomography methods
Radiopharmaceuticals
Brain Neoplasms genetics
Brain Neoplasms metabolism
Brain Neoplasms pathology
Neoplasms, Neuroepithelial genetics
Neoplasms, Neuroepithelial metabolism
Neoplasms, Neuroepithelial pathology
Proto-Oncogene Proteins B-raf genetics
Subjects
Details
- Language :
- English
- ISSN :
- 2051-5960
- Volume :
- 8
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Acta neuropathologica communications
- Publication Type :
- Academic Journal
- Accession number :
- 32811569
- Full Text :
- https://doi.org/10.1186/s40478-020-01023-3