Landscape of Genome-Wide DNA Methylation of Colorectal Cancer Metastasis

• Main Authors: Carmen Ili, Kurt Buchegger, Hannah Demond, Juan Castillo-Fernandez, Gavin Kelsey, Louise Zanella, Michel Abanto, Ismael Riquelme, Jaime López, Tamara Viscarra, Patricia García, Enrique Bellolio, David Saavedra, Priscilla Brebi
• Format: Article
• Language: English
• Published: MDPI AG 2020-09-01
• Series: Cancers
• Subjects: colorectal cancer; metastasis; DNA methylation; lymph node; genome-wide analysis
• Online Access: https://www.mdpi.com/2072-6694/12/9/2710

Colorectal cancer is a heterogeneous disease caused by both genetic and epigenetics factors. Analysing DNA methylation changes occurring during colorectal cancer progression and metastasis formation is crucial for the identification of novel epigenetic markers of patient prognosis. Genome-wide methylation sequencing of paired samples of colon (normal adjacent, primary tumour and lymph node metastasis) showed global hypomethylation and CpG island (CGI) hypermethylation of primary tumours compared to normal. In metastasis we observed high global and non-CGI regions methylation, but lower CGI methylation, compared to primary tumours. Gene ontology analysis showed shared biological processes between hypermethylated CGIs in metastasis and primary tumours. After complementary analysis with The Cancer Genome Atlas (TCGA) cohort, <i>FIGN</i>, <i>HTRA3</i>, <i>BDNF</i>, <i>HCN4</i> and <i>STAC2</i> genes were found associated with poor survival. We mapped the methylation landscape of colon normal tissues, primary tumours and lymph node metastasis, being capable of identified methylation changes throughout the genome. Furthermore, we found five genes with potential for methylation biomarkers of poor prognosis in colorectal cancer patients.