Team C. Proudhon | Circulating (Epi)markers - (E)MC

Background and objectives

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.  

Our team is actively involved in the development of innovative approaches for improved detection and better characterization of circulating analytes. Our goal is to develop new methods detecting epigenetic markers from peripheral blood and to establish more efficient non-invasive tests for cancer diagnosis 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 increase sensitivity. Besides investigating unique genomic regions that are known to be deregulated in cancer genomes, we are also focusing on the deregulation of retrotransposons which accompanies carcinogenesis. These markers could become decisive in detecting residual disease and early stages of multiple forms of cancer.  

Our research has both fundamental and biomedical implications: it should generate in-depth knowledge of the biology of circulating non-genetic tumor biomarkers and help developing more efficient non-invasive diagnostic tests adapted to all types of cancers, based on the universality of these factors.  

Research axes

  • Axis 1 consist of the analysis of circulating DNA methylation profiles
  • Axis 2 aims at analyzing circulating DNA fragmentation patterns to infer its cell-of-origin 
  • Axis 3 investigates circulating transcripts associated with extracellular vesicles

Ultimately, a single test integrating DNA methylation profiles, fragmentation patterns and EV-associated transcripts, from the same plasma sample, could be developed.