Molecular genetic analysis of the REST/NRSF gene in nervous system tumors.
The gene for RE1-silencing transcription factor (REST) alias neuron-restrictive silencer factor NRSF, acts as a transcriptional repressor in the neuronal differentiation pathways in non-neuronal cells, and plays an important role in neuronal development. Inactivating mutations or overexpression of REST have previously been reported in various types of cancer, but no data is available for the role of REST alterations in gliomas. REST gene was screened for mutations in 161 nervous system tumors consisting of astrocytomas, glioblastomas, oligodendrogliomas, oligoastrocytomas, medulloblastomas, meningiomas and schwannomas. REST exons 1-3 were analyzed using denaturing high-performance liquid chromatography (DHPLC) and direct sequencing. The gene copy numbers of REST were investigated by chromogenic (CISH) and fluorescence in situ hybridization (FISH) techniques. Non-synonymous SNPs (P797L, P815S) were found in eight different brain tumor samples. No truncating or activating novel mutations of REST were discovered. Since REST is located at 4q12, a chromosome region implicated in brain tumorigenesis, we conducted gene copy number analyses in medulloblastomas and gliomas. The majority of gliomas (67%) demonstrated low-level amplifications of REST, and only one oligodendroglioma showed high-level amplification of the gene. In medulloblastomas, 38% of samples were determined as aneuploidic, no high-level amplifications were found. Our data suggests that REST is neither activated nor inactivated via mutations in gliomas, while high-level amplification may rarely occur.
Blom
Tea
T
Molecular Cancer Biology Program, University of Helsinki, Biomedicum Helsinki, Haartmaninkatu 8, P.O. Box 180, 00014 Helsinki, Finland.
Tynninen
Olli
O
Puputti
Marjut
M
Halonen
Maija
M
Paetau
Anders
A
Haapasalo
Hannu
H
Tanner
Minna
M
Nupponen
Nina N
NN
D016009:Chi-Square Distribution; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D005091:Exons; D005910:Glioma / Q000235:genetics*; D006801:Humans; D017404:In Situ Hybridization, Fluorescence / Q000379:methods; D008967:Molecular Biology / Q000379:methods; D009423:Nervous System Neoplasms / Q000235:genetics*; D012097:Repressor Proteins / Q000235:genetics*; D014157:Transcription Factors / Q000235:genetics*; D000099229:RE1-Silencing Transcription Factor
D012097:Repressor Proteins; D014157:Transcription Factors; D000099229:RE1-Silencing Transcription Factor