Search

Methylation-based liquid biopsies show promises in detecting cancer using circulating cell-free DNA; however, current limitations impede clinical application. Most assays necessitate substantial DNA inputs, posing challenges. Additionally, underrepresented tumor DNA fragments may go undetected during exponential amplification steps of traditional sequencing methods. Here, we report linear amplification-based bisulfite sequencing (LABS), enabling linear amplification of bisulfite-treated DNA fragments in a genome-wide, unbiased fashion, detecting cancer abnormalities with sub-nanogram inputs. Applying LABS to 100 patient samples revealed cancer-specific patterns, copy number alterations, and enhanced cancer detection accuracy by identifying tissue-of-origin and immune cell composition., (© 2024. The Author(s).)

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.