title: DNA hypermethylation and aberrant expression of the EMP3 gene at 19q13.3 in Human Gliomas.
abstract: Allelic losses on 19q are found in the majority of oligodendroglial tumors and approximately one-third of diffuse astrocytomas. However, the tumor suppressor genes (TSG) on 19q are still elusive. Using cDNA microarray expression profiling, EMP3 at 19q13.3 was among those genes showing the most pronounced expression differences. In line with this, other authors reported EMP3 as being epigenetically silenced in neuroblastomas and astrocytomas. To further investigate EMP3 as a TSG candidate on 19q13.3, we performed molecular analysis of this gene in 162 human gliomas. Mutation analysis did not reveal EMP3 alteration in 132 gliomas. In oligodendroglial tumors, we found that aberrant methylation in the 5'-region of EMP3 was significantly associated with reduced mRNA expression and LOH 19q. In astrocytomas, EMP3 hypermethylation was also paralleled by reduced expression but was independent of the 19q status. EMP3 hypermethylation was detected in more than 80% of diffuse, anaplastic astrocytomas and secondary glioblastomas. Primary glioblastomas, however, mostly lacked EMP3 hypermethylation and frequently overexpressed EMP3. Our data corroborate that oligodendroglial and astrocytic gliomas often show EMP3 hypermethylation and aberrant expression. Furthermore, our findings suggest that primary and secondary glioblastomas are not only characterized by distinct genetic profiles but also differ in their epigenetic aberrations.
authors.affiliation: Department of Neuropathology, Charité, Universitätsmedizin Berlin, D-13353 Berlin, Germany.
authors.forename: Annegret
authors.initials: A
authors.lastname: Kunitz
authors.forename: Marietta
authors.initials: M
authors.lastname: Wolter
authors.forename: Jörg
authors.initials: J
authors.lastname: van den Boom
authors.forename: Jörg
authors.initials: J
authors.lastname: Felsberg
authors.forename: Björn
authors.initials: B
authors.lastname: Tews
authors.forename: Meinhard
authors.initials: M
authors.lastname: Hahn
authors.forename: Axel
authors.initials: A
authors.lastname: Benner
authors.forename: Michael
authors.initials: M
authors.lastname: Sabel
authors.forename: Peter
authors.initials: P
authors.lastname: Lichter
authors.forename: Guido
authors.initials: G
authors.lastname: Reifenberger
authors.forename: Andreas
authors.initials: A
authors.lastname: von Deimling
authors.forename: Christian
authors.initials: C
authors.lastname: Hartmann
mesh_terms: D000328:Adult; D001254:Astrocytoma / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology; D001932:Brain Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000503:physiopathology; D002888:Chromosomes, Human, Pair 19 / Q000235:genetics*; D019175:DNA Methylation; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics*; D020868:Gene Silencing / Q000502:physiology; D020022:Genetic Predisposition to Disease / Q000235:genetics; D005910:Glioma / Q000235:genetics* / Q000378:metabolism / Q000503:physiopathology; D006801:Humans; D008562:Membrane Glycoproteins / Q000096:biosynthesis / Q000235:genetics*; D009837:Oligodendroglioma / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology; D020411:Oligonucleotide Array Sequence Analysis
chemical_list: C485157:EMP3 protein, human; D008562:Membrane Glycoproteins