TY - JOUR
T1 - The CASPR2 cell adhesion molecule functions as a tumor suppressor gene in glioma
AU - Bralten, Linda
AU - Gravendeel, Lonneke
AU - Kloosterhof, Nanne
AU - Sacchetti, Andrea
AU - Vrijenhoek, T
AU - Veltman, JA
AU - van den Bent, Martin
AU - Kros, J.M.
AU - Hoogenraad, CC
AU - Sillevis Smitt, Peter
AU - French, Pim
PY - 2010
Y1 - 2010
N2 - 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. Oncogene (2010) 29, 6138-6148; doi:10.1038/onc.2010.342; published online 16 August 2010
AB - 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. Oncogene (2010) 29, 6138-6148; doi:10.1038/onc.2010.342; published online 16 August 2010
U2 - 10.1038/onc.2010.342
DO - 10.1038/onc.2010.342
M3 - Article
C2 - 20711234
SN - 0950-9232
VL - 29
SP - 6138
EP - 6148
JO - Oncogene
JF - Oncogene
IS - 46
ER -