Oncogenic cell growth linked with hypermethylation of CpG sites within the p53 pathway, and its effects on subgroups

 

  • Authors: Roy Khalife, Ethan Grebler, Anthony Magliocco

  • Presented at: AACR 2025, Chicago IL

  • Journal: Cancer Res (2025) 85 (8_Supplement_1): 229.

  • Publisher: American Association for Cancer Research

  • Publication Date: 4/21/2025

Description:

Methylation of tumor-suppressor genes is a recognized oncogenic mechanism. This study focuses on determining the extent of CpG site methylation within genes of the p53 pathway and assessing how patient sex influences these methylation patterns, which could aid in cancer identification through p53 pathway methylation analysis. Given that mutations in p53 occur in over half of all human cancers, their pro-apoptotic properties are vital for halting unchecked cell growth. We analyzed the methylation status of p53-regulated transcriptional target genes using FFPE samples from various primary brain cancers. Methylation data, generated using the Infinium MethylationEPIC v2.0 array, was visualized through heat maps. Among all samples, the most hypermethylated genes (m-value >2) were identified in descending order as SFN, CASP9, TP53, APAF1, GTSE1, TSC2, and SESN3. Interestingly, TSC2 and SESN3 did not exhibit hypermethylation in male samples, suggesting potential sex-specific epigenetic regulation. The observed trend of hypermethylation—exceeding 80% CpG site methylation—within key inhibitory, apoptotic, and repair genes underscores their silencing and involvement in tumor development. Additionally, the absence of hypermethylation in canonical TP53 targets such as WAF1/p21 highlights the need for further investigation into pathway-specific methylation patterns, potentially uncovering alternative or complementary mechanisms of tumor suppression evasion.

 
Anthony Magliocco