Liquidhope: methylome and genomic profiling from very limited quantities of plasma-derived DNA. Issue 1 (5th January 2023)

• Record Type: Journal Article
• Authors: Trinidad, Eva María; Vidal, Enrique; Coronado, Esther; Esteve-Codina, Anna; Castel, Victoria; Cañete, Adela; Gut, Marta; Heath, Simon; Font de Mora, Jaime
• Is Part Of: Briefings in bioinformatics. Volume 24:Issue 1(2023)
• Publication Date: 2023-01-05
• Subjects: neuroblastoma -- liquid biopsy -- high-risk -- MYCN -- 11q -- DNA methylation -- combined haploinsufficiency; Genetics -- Data processing -- Periodicals; Molecular biology -- Data processing -- Periodicals; Genomes -- Data processing -- Periodicals; 572.80285
• DOI: 10.1093/bib/bbac575
• Languages: English
• ISSNs: 1467-5463

Abstract

Abstract: Analysis of the methylome of tumor cell-free deoxyribonucleic acid (DNA; cfDNA) has emerged as a powerful non-invasive technique for cancer subtyping and prognosis. However, its application is frequently hampered by the quality and total cfDNA yield. Here, we demonstrate the feasibility of very low-input cfDNA for whole-methylome and copy-number profiling studies using enzymatic conversion of unmethylated cysteines [enzymatic methyl-seq (EM-seq)] to better preserve DNA integrity. We created a model for predicting genomic subtyping and prognosis with high accuracy. We validated our tool by comparing whole-genome CpG sequencing with in situ cohorts generated with bisulfite conversion and array hybridization, demonstrating that, despite the different techniques and sample origins, information on cfDNA methylation is comparable with in situ cohorts. Our findings support use of liquid biopsy followed by EM-seq to assess methylome of cancer patients, enabling validation in external cohorts. This advance is particularly relevant for rare cancers like neuroblastomas where liquid-biopsy volume is restricted by ethical regulations in pediatric patients.