An epigenetic signature of advanced colorectal cancer metastasis
Euan J. Rodger,
Gregory Gimenez,
Priyadarshana Ajithkumar,
Peter A. Stockwell,
Suzan Almomani,
Sarah A. Bowden,
Anna L. Leichter,
Antonio Ahn,
Sharon Pattison,
John L. McCall,
Sebastian Schmeier,
Frank A. Frizelle,
Michael R. Eccles,
Rachel V. Purcell,
Aniruddha Chatterjee
Affiliations
Euan J. Rodger
Department of Pathology, Dunedin School of Medicine, University of Otago, Dunedin, New Zealand; Corresponding author
Gregory Gimenez
Department of Pathology, Dunedin School of Medicine, University of Otago, Dunedin, New Zealand
Priyadarshana Ajithkumar
Department of Pathology, Dunedin School of Medicine, University of Otago, Dunedin, New Zealand
Peter A. Stockwell
Department of Pathology, Dunedin School of Medicine, University of Otago, Dunedin, New Zealand
Suzan Almomani
Department of Pathology, Dunedin School of Medicine, University of Otago, Dunedin, New Zealand
Sarah A. Bowden
Department of Pathology, Dunedin School of Medicine, University of Otago, Dunedin, New Zealand
Anna L. Leichter
Department of Pathology, Dunedin School of Medicine, University of Otago, Dunedin, New Zealand
Antonio Ahn
Peter MacCallum Cancer Centre, Melbourne, VIC, Australia; The Sir Peter MacCallum Department of Oncology, Faculty of Medicine, Dentistry and Health Sciences, University of Melbourne, Melbourne, VIC, Australia
Sharon Pattison
Department of Medicine, Dunedin School of Medicine, University of Otago, Dunedin, New Zealand
John L. McCall
Department of Surgical Sciences, Dunedin School of Medicine, University of Otago, Dunedin, New Zealand
Sebastian Schmeier
Evotec SE, Hamburg, Germany
Frank A. Frizelle
Department of Surgery, University of Otago, Christchurch, New Zealand
Michael R. Eccles
Department of Pathology, Dunedin School of Medicine, University of Otago, Dunedin, New Zealand
Rachel V. Purcell
Department of Surgery, University of Otago, Christchurch, New Zealand; Corresponding author
Aniruddha Chatterjee
Department of Pathology, Dunedin School of Medicine, University of Otago, Dunedin, New Zealand; Honorary Professor, School of Health Sciences and Technology, UPES University, India; Corresponding author
Summary: Colorectal cancer (CRC) is a leading cause of morbidity and mortality worldwide. The majority of CRC deaths are caused by tumor metastasis, even following treatment. There is strong evidence for epigenetic changes, such as DNA methylation, accompanying CRC metastasis and poorer patient survival. Earlier detection and a better understanding of molecular drivers for CRC metastasis are of critical clinical importance. Here, we identify a signature of advanced CRC metastasis by performing whole genome-scale DNA methylation and full transcriptome analyses of paired primary cancers and liver metastases from CRC patients. We observed striking methylation differences between primary and metastatic pairs. A subset of loci showed coordinated methylation-expression changes, suggesting these are potentially epigenetic drivers that control the expression of critical genes in the metastatic cascade. The identification of CRC epigenomic markers of metastasis has the potential to enable better outcome prediction and lead to the discovery of new therapeutic targets.
