The CASPR2 cell adhesion molecule functions as a tumor suppressor gene in glioma.
Genomic translocations have been implicated in cancer. In this study, we performed a screen for genetic translocations in gliomas based on exon-level expression profiles. We identified a translocation in the contactin-associated protein-like 2 (CASPR2) gene, encoding a cell adhesion molecule. CASPR2 mRNA was fused to an expressed sequence tag that likely is part of the nuclear receptor coactivator 1 gene. Despite high mRNA expression levels, no CASPR2 fusion protein was detected. In a set of 25 glioblastomas and 22 oligodendrogliomas, mutation analysis identified two additional samples with genetic alterations in the CASPR2 gene and all three identified genetic alterations are likely to reduce CASPR2 protein expression levels. Methylation of the CASPR2 gene was also observed in gliomas and glioma cell lines. CASPR2-overexpressing cells showed decreased proliferation rates, likely because of an increase in apoptosis. Moreover, high CASPR2 mRNA expression level is positively correlated with survival and is an independent prognostic factor. These results indicate that CASPR2 acts as a tumor suppressor gene in glioma.
Bralten
L B C
LB
Department of Neurology, Erasmus Medical Center, Rotterdam, The Netherlands.
Gravendeel
A M
AM
Kloosterhof
N K
NK
Sacchetti
A
A
Vrijenhoek
T
T
Veltman
J A
JA
van den Bent
M J
MJ
Kros
J M
JM
Hoogenraad
C C
CC
Sillevis Smitt
P A E
PA
French
P J
PJ
D001932:Brain Neoplasms / Q000235:genetics*; D002465:Cell Movement; D049109:Cell Proliferation; D019175:DNA Methylation; D016147:Genes, Tumor Suppressor; D005910:Glioma / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics* / Q000502:physiology; D009154:Mutation; D009361:Neoplasm Invasiveness; D009419:Nerve Tissue Proteins / Q000235:genetics* / Q000502:physiology; D056920:Nuclear Receptor Coactivator 1 / Q000502:physiology; D012333:RNA, Messenger / Q000032:analysis
C403049:CNTNAP2 protein, human; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D012333:RNA, Messenger; C538859:NCOA1 protein, human; D056920:Nuclear Receptor Coactivator 1