Exon 4 and intron 4 TP53 are both methylated in advanced-stage ovarian carcinomas

Although intragenic CpG dinucleotides are conserved during evolution, they are also sensitive to methylation-dependent mechanisms. Methylation status of the TP53 introns 1, 3 and 4 have been analysed in stage III ovarian carcinoma (OC). In the present study, the methylation of exon 4 (10 CpG pairs) was analysed in advanced-stage OC to investigate TP53 methylation and compare exon and intron 4 methylation patterns. A total of 80 samples from patients with advanced-stage OC and metastatic lesions were examined, along with 80 samples derived from healthy patients who had never been diagnosed with cancer. Methylation analysis of the human A2780 ovarian cancer cell line was also performed. Exon and intron 4 were methylated in OC, corresponding metastases and paired healthy tissue. The DNA from the human A2780 ovarian cancer cell line and the normal samples from healthy subjects was also methylated. The data indicate the existence of an intragenic mechanism of regulation of TP53 activity that involves demethylation/methylation processes. This mechanism provides the ability to alter the response from cell cycle arrest to apoptosis by manipulating only the expression of long or short p53 isoforms.