Transcriptional inactivation of TP73 expression in oligodendroglial tumors

The TP73 gene, located on chromosome Ip36.3, 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 Ip36.3. 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. (C) 2002 Wiley-Liss, Inc.