EpiDetect · Detecting epigenetic biomarkers in the blood for non-invasive precision oncology

The detection of circulating tumor DNA allows to non-invasively retrieve tumor molecular profiles and follow disease evolution. These approaches promise optimal and individualized management of patients with cancer. However, despite remarkable progress, several technological obstacles still limit liquid biopsy widespread application. Indeed, detecting small fractions of tumor DNA released when the tumor burden is reduced remains a challenge. Samples collected at early stages or during treatment may contain less than one mutant copy per milliliter of plasma, which is below the detection limit of current technologies. Moreover, detectable recurrent mutations do not cover all patients. It is therefore necessary to develop new, more sensitive, but also more informative tools. My goal is to develop new methods detecting epigenetic markers from peripheral blood for establishing more efficient non-invasive diagnostic tests and disease monitoring. Targeting the cancer epigenome, which contains a myriad of somatic alterations that do not modify the DNA sequence and cover cases without detectable mutations, will achieve increased sensitivity. These markers could become decisive in detecting residual disease and early stages of multiple forms of cancer. I will develop approaches to: 1) Analyze circulating DNA methylation profiles at unique and repeated sequences; 2) Identify circulating DNA cells of origin using nucleosome footprint; 3) Analyze transcripts associated with circulating extracellular vesicles. Ultimately, a single test integrating DNA methylation profiles, fragmentation patterns and EV-associated transcripts, from the same plasma sample, will be developed.This project has both fundamental and biomedical implications: it will generate in-depth knowledge of the biology of circulating non-genetic tumor biomarkers and lead to the development of more efficient non-invasive diagnostic tests adapted to all types of cancers, based on the universality of these factors.