Transcriptional inactivation of TP73 expression in oligodendroglial tumors.
The TP73 gene, located on chromosome 1p36.3, encodes a product that shares significant structural homology with the tumor suppressor TP53. The aim of this study was to investigate whether TP73 is involved in the development of oligodendroglial tumors, which frequently carry deletions involving 1p36.3. Semi-quantitative reverse transcription-polymerase chain reaction was used to determine TP73 transcript levels. Ten of 24 (42%) tumors showed negligible to more than 5-fold reduction in TP73 expression when compared to normal brain level. To identify potential mechanisms that may modulate TP73 transcription in oligodendroglial tumors, we performed mutation analysis on the TP73 gene. No somatic mutations were however detected in the gene sequence. We then evaluated the possible involvement of epigenetic change in TP73 expression. Bisulfite genomic sequencing detected aberrant hypermethylation at the 5' region upstream and including the first exon of the TP73 gene in 17 of 44 (39%) oligodendroglial tumors, whereas normal brain tissues showed no methylation in the same region examined. Moreover, 6 of 10 (60%) tumors with negligible or decreased levels of TP73 transcripts were methylation-positive. In conclusion, our results showed that inactivation of TP73 occurs at the transcriptional level and is associated with promotor hypermethylation. Loss of or reduced TP73 transcript expression may contribute to the tumorigenesis of oligodendroglial tumors.
Dong
Shumin
S
Department of Anatomical and Cellular Pathology, Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong.
Pang
Jesse Chung-sean
JC
Hu
Jie
J
Zhou
Liang-fu
LF
Ng
Ho-keung
HK
D000293:Adolescent; D000328:Adult; D000368:Aged; D001254:Astrocytoma / Q000235:genetics*; D001932:Brain Neoplasms / Q000235:genetics* / Q000473:pathology; D002648:Child; D018899:CpG Islands / Q000235:genetics; D019175:DNA Methylation; D004252:DNA Mutational Analysis; D017931:DNA Primers / Q000737:chemistry; D004273:DNA, Neoplasm / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics*; D005260:Female; D020868:Gene Silencing; D016147:Genes, Tumor Suppressor; D006801:Humans; D008297:Male; D008875:Middle Aged; D009687:Nuclear Proteins / Q000235:genetics*; D009837:Oligodendroglioma / Q000235:genetics* / Q000473:pathology; D016133:Polymerase Chain Reaction; D018807:Polymorphism, Single-Stranded Conformational; D012333:RNA, Messenger / Q000378:metabolism; D014158:Transcription, Genetic; D000072160:Tumor Protein p73; D025521:Tumor Suppressor Proteins
D017931:DNA Primers; D004273:DNA, Neoplasm; D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; D012333:RNA, Messenger; C000606460:TP73 protein, human; D000072160:Tumor Protein p73; D025521:Tumor Suppressor Proteins