Progress toward liquid biopsies in pediatric solid tumors

Abstract

Pediatric solid tumors have long been known to shed tumor cells, DNA, RNA, and proteins into the blood. Recent technological advances have allowed for improved capture and analysis of these typically scant circulating materials. Efforts are ongoing to develop "liquid biopsy" assays as minimally invasive tools to address diagnostic, prognostic, and disease monitoring needs in childhood cancer care. Applying these highly sensitive technologies to serial liquid biopsies is expected to advance understanding of tumor biology, heterogeneity, and evolution over the course of therapy, thus opening new avenues for personalized therapy. In this review, we outline the latest technologies available for liquid biopsies and describe the methods, pitfalls, and benefits of the assays that are being developed for children with extracranial solid tumors. We discuss what has been learned in several of the most common pediatric solid tumors including neuroblastoma, sarcoma, Wilms tumor, and hepatoblastoma and highlight promising future directions for the field.

Keywords: Cell-free DNA; Epigenetics; Liquid biopsy; Next-generation sequencing; Pediatric solid tumors.

Figure 1:. Overview of approaches to capturing and investigating circulating analytes from liquid biopsies.

In the presence of malignancy, a liquid biopsy (i.e., blood) has been demonstrated to contain single tumor cells, free nucleic acids, exosomes containing nucleic acids and proteins, and free circulating nucleosomes. These components, sampled by simple phlebotomy, can be analyzed to detect single nucleotide mutations, copy number aberrations, fusions, translocations, and epigenetic changes reflective of tumor genetic heterogeneity. Abbreviations: cfDNA, cell free DNA; ctDNA, circulating tumor DNA; qPCR, quantitative PCR; RT-qPCR, quantitative reverse transcription PCR; WES, whole exome sequencing; WGS, whole genome sequencing.