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Molecular Cloning of a Gene Disrupted by a Balanced
Translocation in a Meningioma
Ronald H. Lekanne Deprez', Peter H.J. Riegman*, Nicole A. Groen', Ursula L.
Warringa*, Nick A. van Biezen*, Aneo Molijn*, Dirk Bootsma#, Pieter de Jong@, Anil
Menon#, Nikolai Kley$, Bernd R. Seizinger$, and Ellen C. Zwarthoff*
Departments of *Pathology and Heel! Biology and Genetics, Erasmus University, Rotterdam; @Human Genome
Center, Lawrence Livermore National Laboratory, University of California, Livermore, California; HDepartrnent
of Molecular Genetics, University of Cincinnati Medical Center; $Oncology Drug Discovery, Department of
Molecular Genetics and Cell Biology, Bristol Myers-Squibb Pharmaceutical Research Institute, Princeton
Abstract
We have previously mapped a putative meningioma suppressor gene at the chromosome
22 breakpoint of a t(4;22)(pI6;qll), which was observed in meningioma 32. We now
report the isolation of a gene (MNl) from chromosome 22, which is disrupted by the
translocation breakpoint. The MNI gene spans about 70 kb and consists of at least two
large exons of approximately 4.7 kb and 2.8 kb. The 4.7 kb exon is disl'upted by the
t(4;22). TIlere is no obvious homology in the nucleotide and putative amino acid
sequences with other Imown genes. The gene is highly conserved in evolution and
nOl1hern blots show a ubiquitously expressed mRNA of 8 kb with an alternative 4.5 kb
transcript in skeletal muscle. In meningiomas the expression pattel'll is very variable.
Some, including meningioma 32, show no expression suggesting that the gene could
fUllction as a tumor suppressor gene fol' meningeal cells. Paradoxically, howevel', a very
high expression is sometimes also observed in meningiomas.
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