Analysis of the NF2 tumor-suppressor gene and of chromosome 22 deletions in gliomas.
Recurrent deletions of chromosome fragments observed in neoplasms are thought to participate in tumor development through the inactivation of tumor-suppressor genes. In gliomas, the most frequent deletions involve chromosome arms 9p, 10q, 17p, 19q and 22q. We have analysed deletions of chromosome 22 in gliomas by studying loss of heterozygosity (LOH) at 8 microsatellite loci. LOH for this chromosome fragment was observed in 17/70 (24%) cases, most of them encompassing the region which encodes the gene altered in neurofibromatosis 2 (NF2), an inherited disease which predisposes to tumors of the nervous system. To investigate the possible involvement of the NF2 tumor-suppressor gene in the tumorigenesis of gliomas, we searched for alterations in its genomic structure and in its mature transcript. Northern-blot and reverse transcriptase-PCR experiments showed that the NF2 transcript is expressed and does not demonstrate obvious structural alterations. Moreover, analysis, at the genomic level, of the 16 coding exons of the NF2 gene by denaturing gradient gel electrophoresis failed to detect any somatically acquired point mutations. Altogether, these data strongly suggest that, although gliomas demonstrate recurrent chromosome 22 deletions most frequently encompassing the NF2 region, the NF2 gene is not altered in these tumors.
Hoang-Xuan
K
K
Laboratoire de Génétique des Tumeurs, INSERM CJF 9201, Institut Curie, Paris, France.
Merel
P
P
Vega
F
F
Hugot
J P
JP
Cornu
P
P
Delattre
J Y
JY
Poisson
M
M
Thomas
G
G
Delattre
O
O
D001483:Base Sequence; D015152:Blotting, Northern; D002872:Chromosome Deletion; D002892:Chromosomes, Human, Pair 22 / Q000235:genetics*; D004252:DNA Mutational Analysis; D017931:DNA Primers; D004273:DNA, Neoplasm / Q000235:genetics; D004276:DNA, Satellite / Q000235:genetics; D004591:Electrophoresis, Polyacrylamide Gel / Q000379:methods; D017353:Gene Deletion; D016515:Genes, Neurofibromatosis 2; D005910:Glioma / Q000235:genetics*; D006579:Heterozygote; D006801:Humans; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction / Q000379:methods
D017931:DNA Primers; D004273:DNA, Neoplasm; D004276:DNA, Satellite