Abstract 2163: Circulating H3K27 nucleosomes to monitor lung cancer patients during treatment, a universal biomarker quantifying the molecular residual disease (MRD) in plasma samples

Introduction: Treatment options of lung cancer (LC) comprise radiotherapy, and/or combined treatment approaches, including chemotherapy, immunotherapy and targeted therapies based on the tumoral molecular profile. Following curative-intent first-line therapies, clinical surveillance involves serial CT imaging. However, such surveillance can detect only macroscopic disease recurrence and is frequently inconclusive. NGS has been utilized to help identify and monitor treatment plans. Nucleosomes, complexes of DNA and histones proteins, are released during cell death into blood circulation. Trimethylation of lysine 27 on histone H3 (H3K27Me3), catalyzed by enhancer of zeste homolog 2 (EZH2), is a crucial epigenetic process in tumorigenesis. We investigated if H3K27Me3-nucleosome concentration could be a biomarker for molecular residual disease (MRD). Patients and Methods: Plasmas were retrospectively collected from patients with advanced LC during treatment (CIRCAN’s cohort, n= 200) and from healthy donors (n=100). We carried out standard targeted NGS on paired plasmas. Samples were divided in two sub-groups based on genetical results: ctDNA negative (n=120) or positive (n=80) for presence of somatic alterations. Concentration of circulating H3K27Me3-nucleosome was measured using chemiluminescent Nu.Q® immunoassay (Belgian Volition SRL, Belgium). Results: Significantly elevated concentrations of H3K27Me3-nucleosomes were found in LC plasmas during the follow-up of patients compared to healthy donors (median 14.9 ng/ml vs 6.15 ng/ml, respectively, p