Human Molecular Genetics, Vol 7, 1859-1872, Copyright © 1998 by Oxford University Press
D Heckel, N Comtesse, N Brass, N Blin, KD Zang and E Meese
By screening a meningioma expression library with autologous serum we
identified four cDNA clones representing a novel gene with striking
homology to Caenorhabditis elegans hyaluronidase as indicated by BLASTP
analysis. In humans hyaluronidase has been implicated in cancer development
and three human genes are known to encode proteins with hyaluronidase
activity. None of the human genes, however, showed any homology at the
nucleotide or amino acid sequence level to the newly isolated antigen we
termed meningioma expressed antigen 5 (MGEA5). Somatic cell hybrid mapping
and fluorescence in situ hybridization mapped the gene for MGEA5 to
chromosomal band 10q24.1-q24.3. Reverse transcription (RT)-PCR and northern
blot hybridization revealed expression of the gene encoding MGEA5 in
several meningioma and additional human tissues. Expression analysis also
indicated an alternative splicing event giving rise to a shorter and
altered transcript termed MGEA5s. The expression of MGEA5 and MGEA5s as
fusion proteins revealed an approximate molecular weight of 92 and 54 kDa,
respectively. Using heterologous sera we found antibodies against MGEA5s in
five out of 23 meningioma patients, whereas no immune reaction was detected
in 12 control sera from healthy individuals. Confirmation of hyaluronidase
activity was independently achieved by turbidometric analysis and a gel
matrix assay. A model for involvement of the novel hyaluronidase gene in
meningioma development is proposed.
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Novel immunogenic antigen homologous to hyaluronidase in meningioma
Institut fur Humangenetik, Theoretische Medizin, Universitat des Saarlandes, 66421 Homburg/Saar, Germany.
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