Novel immunogenic antigen homologous to hyaluronidase in meningioma.
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.
Heckel
D
D
Institut für Humangenetik, Theoretische Medizin, Universität des Saarlandes, 66421 Homburg/Saar, Germany.
Comtesse
N
N
Brass
N
N
Blin
N
N
Zang
K D
KD
Meese
E
E
D000118:Acetylglucosaminidase; D017398:Alternative Splicing; D000595:Amino Acid Sequence; D000951:Antigens, Neoplasm; D001483:Base Sequence; D002874:Chromosome Mapping; D002879:Chromosomes, Human, Pair 10 / Q000235:genetics; D018076:DNA, Complementary / Q000737:chemistry / Q000235:genetics; D019143:Evolution, Molecular; D014644:Genetic Variation; D051548:Histone Acetyltransferases; D006801:Humans; D006821:Hyaluronoglucosaminidase / Q000235:genetics*; D017404:In Situ Hybridization, Fluorescence; D008579:Meningioma / Q000201:enzymology* / Q000235:genetics*; D008969:Molecular Sequence Data; D009363:Neoplasm Proteins / Q000235:genetics*; D016366:Open Reading Frames; D016415:Sequence Alignment; D017422:Sequence Analysis, DNA; D017386:Sequence Homology, Amino Acid; D012689:Sequence Homology, Nucleic Acid; D001619:beta-N-Acetylhexosaminidases
D000951:Antigens, Neoplasm; D018076:DNA, Complementary; D009363:Neoplasm Proteins; D051548:Histone Acetyltransferases; C115866:OGA protein, human; D006821:Hyaluronoglucosaminidase; D000118:Acetylglucosaminidase; D001619:beta-N-Acetylhexosaminidases