The Cancer Genetics and Epigenetics group studies alterations that impact the development of colorectal cancer (CRC) and gastric cancer, as well as their corresponding tumour phenotypes.

Their studies have extensively investigated DNA hypomethylation of genes and repetitive elements in the very early steps of gastrointestinal carcinogenesis, identifying that aberrant genomic demethylation of the mucosa is a risk factor for gastric and colorectal cancer development. They have also found that hypomethylation of some specific repetitive DNA elements is associated with aberrant genome duplication, which is known to promote chromosomal instability and contribute to the development of gastrointestinal cancers.

The current research of the group aims to explore the molecular mechanisms underlying this association between hypomethylation of those repetitive DNA elements and aberrant genomic duplication, which could reveal fundamental factors in the early stages of tumorigenesis preceding malignant transformation.

The group is also studying epigenetic alterations associated with CRC immunogenicity. Their recent studies have revealed the association between the epigenetic silencing of genes encoding extracellular matrix remodelers and higher lymphocytic infiltration levels in non-hypermutant CRCs. Pharmacological inhibition of these extracellular matrix remodelers could increase tumour immunogenicity, resulting in more abundant lymphocytic infiltration and enhanced response to immune checkpoint inhibitor therapy. This research builds on the group's long-standing interest in DNA methylation alterations affecting extracellular matrix remodelers, which led to the discovery of frequent and coordinated hypermethylation of ADAMTS genes. Additionally, their research has identified methylation alterations in other genes that have a substantial impact on CRC phenotype, they developed microarray-based technologies to analyse genomic methylation and discovered highly specific and sensitive epigenetic biomarkers for biliary cancer detection.

In their research, the team employs an interdisciplinary approach that combines epigenomics, transcriptomics, and genomics, computational analysis, molecular biology, and cell biology. Over the past few years, the group has been actively developing novel, cost-efficient, and scalable in vitro immuno-oncology models for genetic and pharmacological studies aimed at enhancing tumour immunogenicity and improving the response of gastrointestinal cancers to the most recently developed immunotherapies.

Keywords: Epigenomics, gastrointestinal cancer, immuno-oncology, 3D in vitro models.