Abstract 20P
Background
Genetic factors have long been acknowledged as pivotal contributors in cancer development. Emerging evidence highlights the critical role of epigenetic variations in shaping chromatin stability, gene expression, and cellular responsiveness, thus intricately influencing cancer progression. This study aims to achieve three specific goals: first, the identification of cancer-specific differentially methylated regions; second, an exploration of the effects epigenetic modification on cellular behaviour in in vitro breast cancer models; and third, an assessment of the persistence of chromatin state changes which followed the epigenetic changes that were introduced.
Methods
Our study identifies cancer-specific targets using Cancer Genome Atlas (TCGA) DNA methylation datasets and the EpiMark dataset from the International Agency for Research on Cancer (IARC). Differentially methylated sites were determined by comparing DNA methylation levels between tumour and non-tumour tissue in the IARC datasets and the EpiMark datasets separately. dCas9-based epigenetic tools were used to induce the observed changes in vitro models of breast cancer to explore the impact of reversing cancer-specific DNA methylation patterns on cell viability, invasiveness, and clonogenicity. Finally, the persistence of chromatin state changes induced by dCas9-coupled systems in vitro will be evaluated.
Results
Preliminary analysis of the TCGA and Epimark databases reveals commonly methylated differentially methylated regions (DMRs) between breast tumour and non-tumour tissues, with sites linked to genes emerging as promising candidates for epigenetic editing. Genes associated with these sites included POLR1D, LNX2, CLCC1, TLDC1, FOLR1, RAB3IP, MYRFL, HAGLROS, HOXD1, MIR7704, HAGLR, and HOXD3. These sites exhibit significant associations with altered survival in breast cancer patients from the TCGA dataset.
Conclusions
This work will showcase the application of epigenomic methods for the targeted modification of cancer-specific epigenetic changes and will allow for the unambiguous elucidation of cancer-specific epigenetic modifications on cellular behaviour.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
Sunway University.
Funding
International Agency for Research on Cancer (IARC).
Disclosure
All authors have declared no conflicts of interest.