Circulating Histones to Detect and Monitor the Progression of Cancer

Liquid biopsies have emerged as a minimally invasive cancer detection and monitoring method, which could identify cancer-related alterations in nucleosome or histone levels and modifications in blood, saliva, and urine. Histones, the core component of the nucleosome, are essential for chromatin compaction and gene expression modulation. Increasing evidence suggests that circulating histones and histone complexes, originating from cell death or immune cell activation, could act as promising biomarkers for cancer detection and management. In this review, we provide an overview of circulating histones as a powerful liquid biopsy approach and methods for their detection. We highlight current knowledge on circulating histones in hematologic malignancies and solid cancer, with a focus on their role in cancer dissemination, monitoring, and tumorigenesis. Last, we describe recently developed strategies to identify cancer tissue-of-origin in blood plasma based on nucleosome positioning, inferred from nucleosomal DNA fragmentation footprint, which is independent of the genetic landscape.

Automated summary

Liquid biopsies have emerged as a minimally invasive method for detecting and monitoring cancer, using blood, saliva, and urine to identify cancer-related alterations in nucleosome or histone levels and modifications. Circulating histones and histone complexes have shown promise as biomarkers for cancer detection and management, originating from cell death or immune cell activation. This review provides an overview of circulating histones as a powerful liquid biopsy approach, highlighting their role in hematologic malignancies and solid cancer, as well as strategies for their detection and identification of cancer tissue-of-origin in blood plasma.