Retention of imprinting of the human apoptosis-related gene TSSC3 in human brain tumors.
Genomic imprinting is the result of a gamete-specific modification leading to parental origin-specific gene expression in somatic cells of the offspring. Several embryonal tumors show loss of imprinting of genes clustered in human chromosome 11p15.5, an important tumor suppressor gene region, harboring several normally imprinted genes. TSSC3, a gene homologous to mouse TDAG51, implicated in Fas-mediated apoptosis, is also located in this region between hNAP2 and p57 (KIP2). TSSC3 is the first apoptosis-related gene found to be imprinted in placenta, liver and fetal tissues where it is expressed from the maternal allele in normal human development. This study investigated the imprinting status of TSSC3 in human normal, adult brain and in human neuroblastomas, medulloblastomas and glioblastomas. A polymorphism in exon 1 at position 54 was used to analyze the allelic expression of the TSSC3 gene by a primer oligo base extension (PROBE) assay using matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS). We found that the TSSC3 gene is not imprinted in human normal, adult brain and blood. In contrast, strong allelic bias resembling imprinting could be detected in most examined tumor specimens. The results demonstrate for the first time that the tumors under investigation are associated with a retention of imprinting of a potential growth inhibitory gene.
Müller
S
S
University Hospital Eppendorf, Department of Neurosurgery, Hamburg, Germany.
van den Boom
D
D
Zirkel
D
D
Köster
H
H
Berthold
F
F
Schwab
M
M
Westphal
M
M
Zumkeller
W
W
D000818:Animals; D017209:Apoptosis / Q000235:genetics*; D001483:Base Sequence; D001921:Brain / Q000378:metabolism; D001932:Brain Neoplasms / Q000235:genetics* / Q000473:pathology; D019175:DNA Methylation / Q000187:drug effects; D017931:DNA Primers; D018392:Genomic Imprinting; D006801:Humans; D051379:Mice; D009687:Nuclear Proteins / Q000097:blood / Q000235:genetics*; D014407:Tumor Cells, Cultured
D017931:DNA Primers; D009687:Nuclear Proteins; C109277:TSSC3 protein