Abstract
Abstract
Colorectal cancer (CRC) is one of the biggest cause of death world-wide and the second-highest cause of death by cancer in New Zealand with a mortality rate of approximately four deaths/day and 90% of CRC-associated mortality is caused by metastasis. Development of metastasis and the modifications that occur during various stages in the CRC metastatic cascade remains obscure. Emerging evidence indicates that epigenetic alterations have a greater influence on the development of metastasis than genetic mutations, but the current understanding of epigenetic drivers that cause CRC metastasis is limited. In the current project, as a first step in identifying epigenetic drivers for metastasis, whole-genome methylation and transcriptome profiles from paired primary and metastatic samples from the same NZ patients will be compared. Subsequently, the epigenetic drivers will be validated, and it can potentially be used as CRC metastatic markers. Circulating tumour cells (CTCs) represent the conduit between primary and metastatic tumours. They could be used to identify driver epigenetic changes associated with epithelial-to-mesenchymal transition (EMT), migration and invasion which occur during the metastatic cascade. CTCs are obtained from the blood and would provide a clinically less invasive test rather than requiring tissue samples. The recent development of single-cell sequencing technologies has now made it feasible to identify epigenetic changes in individual CTCs. In the second part of this project, protocols for single-cell DNA methylation and expression analysis will be developed using human colon cancer cell lines as a model. These optimised protocols will then be applied to CTCs from patient blood samples to identify epigenetic changes that predispose patients to metastasis. Identification of epigenetic drivers will help to detect individuals at high risk for metastasis prior to metastasis being clinically apparent, allowing for more personalised treatment and contribute to improving survival.
Citation Format: Aniruddha Chatterjee, John McCall, Parry Guilford, Sharon Pattison, Euan Rodger, Priyadarshana Ajithkumar. Epigenomic profiling of colorectal cancer to predict patients at high risk of metastasis [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 2434.