Characterization of a gene which is disrupted by a balanced translocation in a meningioma
- Erasmus Univ., Rotterdam (Netherlands); and others
Meningiomas are tumors of the central nervous system in which loss of heterozygosity for markers on the long arm of chromosome 22 is a frequent event. We have previously described a balanced t(4;22)(p16;q11), which was observed in meningioma 32. We have cloned a gene (MN1), which is disrupted by the translocation breakpoint. The gene spans about 70 kb on chromosome 22q11. A total of 7.5 kb of overlapping cDNA clones were isolated. A comparison of the cDNA clones with the genomic cosmid contig from this region shows that the MN1 gene consists of at least two large exons of approximately 4.7 kb and 2.8 kb. Sequence analysis of the MN1 cDNA revealed two open reading frames (ORFs) of 1 and 2.3 kb which are separated by a region of approximately 1 kb with stop codons in all reading frames. The second ORF is disrupted by the t(4;22) translocation. In the region between the ORFs 2 CAG repeats have been found. These repeats do not display length variation in meningiomas. There is no obvious homology in the nucleotide and putative amino acid sequences with other known genes. The MN1 gene is highly conserved in evolution. The approximately 8 kb MN1 mRNA is ubiquitously expressed with an alternative 4.5 kb transcript in skeletal muscle. In meningiomas the expression pattern is very variable and a 6.5 kb transcript is sometimes also observed. Some, including meningioma 32, show no expression suggesting that the gene could function as a tumor suppressor gene for meningeal cells. Paradoxically, however, a very high expression is sometimes also observed in meningiomas.
- OSTI ID:
- 133337
- Report Number(s):
- CONF-941009--
- Journal Information:
- American Journal of Human Genetics, Journal Name: American Journal of Human Genetics Journal Issue: Suppl.3 Vol. 55; ISSN AJHGAG; ISSN 0002-9297
- Country of Publication:
- United States
- Language:
- English
Similar Records
Alternative processing of mRNAs encoding mammalian chromosomal high-mobility-group proteins HMG-I and HMG-Y
Construction of a 2.8-megabase yeast artificial chromosome contig and cloning of the human methylthioadenosine phosphorylase gene from the tumor suppressor region on 9p21