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Loss
of heterozygosity on chromosome 22 in human gliomas does not inactivate the
neurofibromatosis type 2 gene
Watkins D, Ruttledge MH, Sarrazin J, Rangaratnam S, Poisson M, Delattre JY,
Rouleau GA
Department of Medicine, McGill University, Montreal General
Hospital Research Institute, Quebec, Canada.
The molecular genetic alterations that underlie development of gliomas, the most
common neoplasm of the human central nervous system, include activation of
cellular proto-oncogenes as well as inactivation of tumor suppressor
genes.
Although research has identified some affected loci, others clearly remain to be
identified.
We have investigated loss of heterozygosity on chromosome 22 in a panel of
sporadic gliomas, and have assessed the possibility that inactivation of the
neurofibromatosis type 2 (NF2) tumor suppressor gene on 22q plays a role in
development of sporadic gliomas in humans.
Loss of heterozygosity for loci on chromosome 22 loci was observed in 15 of 47
informative blood-tumor pairs, although no common area of loss of heterozygosity
shared by all of these tumors could be identified.
The most frequently affected segment, distal to the NF2 locus and bounded
proximally by D22S15 and distally by a gene for myoglobin, was shared by as many
as 11 tumors.
Loss of heterozygosity at the NF2 locus was observed in 10 tumors.
No rearrangements of the NF2 gene could be detected by Southern analysis of
restriction endonuclease-digested genomic DNA, and no abnormally migrating bands
were detected on single strand conformation analysis of individual exons of the
NF2 gene.
Thus, although frequent loss of heterozygosity on chromosome 22 suggests that
inactivation of a tumor suppressor gene on this chromosome plays a role in
development of gliomas, there is no evidence that inactivation of the NF2 gene
is implicated in this process, confirming the results of other studies of the
NF2 gene in human gliomas.
The identity of the putative tumor suppressor gene on 22q involved in
development of gliomas remains unknown.
PMID: 8956876 [PubMed - indexed for MEDLINE]
Source: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8956876&dopt=Abstract
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