Global DNA hypomethylation increases with patient age and correlates with genomic damage in gastrointestinal cancers (Suzuki et al, Cancer Cell, 2006). This result led us to propose a "wear and tear" model linking aging and... [ view full abstract ]
Global DNA hypomethylation increases with patient age and correlates with genomic damage in gastrointestinal cancers (Suzuki et al, Cancer Cell, 2006). This result led us to propose a "wear and tear" model linking aging and cancer by the unavoidable progressive erosion of genomic DNA methylation during aging. Two examples of “severe” DNA demethyation (higher than the average) did not comply with the “wear & tear” model.
Searching for biomarkers of multiple colon cancer (CC), we found that low levels of LINE-1 methylation (a surrogate marker of global levels of DNA methylation) correlated with the presence of synchronous CC and were predictive of high risk for developing metachronous tumors (Kamiyama et al., Oncogene, 2012). Thus, demethylation level can be used as prognostic biomarker for metachronous CC high risk. Among the patients with “severe” demethylation, those with multiple tumors were younger, supporting a role of genetic factors in multiple tumor risk.
In 22% of CC, a pericentromeric macrosatellite (SST1/NBL2), was found hypomethylated, of which 7% exhibited a “severe” hypomethylation (more than 10%) that co-occurred with TP53 mutations in relatively younger patients (Samuelsson et al, Epigenomes, 2016). SST1/NBL2 is expressed as a novel long non-coding RNA that forms perinucleolar aggregates in a tight mirror image structure with SAM68 nuclear bodies (Dumbović et al, NAR, 2018), the function of which is under study.
The Genomes for Life (GCAT) is a long-term prospective cohort study ongoing at our institution that aims to explore the role of epidemiologic, environmental, genomic, and epigenomic factors in the development of cancer and other chronic diseases in Catalonia. The GCAT project has recruited near 20.000 participants at the end of 2017. Volunteers complete a detailed epidemiological questionnaire and undergo anthropometry measurements, and plasma, serum, and white blood cells are collected. The GCAT study has access to the Electronic Health Records (EHR) of the Catalan Public Health Care System. Participants will be followed at least 20 years after recruitment. Genomic and epigenomic analyses are being performed to investigate the association of epidemiologic, environmental and genetic risk factors with (multiple) CC and other cancers and chronic diseases.
Biomarkers and diagnostics, liquid biopsy, imaging, biochip/microarray technologies, advan
