RESUMO
Cell-free DNA (cfDNA) can be isolated and sequenced from blood and/or urine of cancer patients. Conventional short-read sequencing lacks deployability and speed and can be biased for short cfDNA fragments. Here, we demonstrate that with Oxford Nanopore Technologies (ONT) sequencing we can achieve delivery of genomic and fragmentomic data from liquid biopsies. Copy number aberrations and cfDNA fragmentation patterns can be determined in less than 24 h from sample collection. The tumor-derived cfDNA fraction calculated from plasma of lung cancer patients and urine of bladder cancer patients was highly correlated (R = 0.98) with the tumor fraction calculated from short-read sequencing of the same samples. cfDNA size profile, fragmentation patterns, fragment-end composition, and nucleosome profiling near transcription start sites in plasma and urine exhibited the typical cfDNA features. Additionally, a high proportion of long tumor-derived cfDNA fragments (> 300 bp) are recovered in plasma and urine using ONT sequencing. ONT sequencing is a cost-effective, fast, and deployable approach for obtaining genomic and fragmentomic results from liquid biopsies, allowing the analysis of previously understudied cfDNA populations.
Assuntos
Ácidos Nucleicos Livres , Neoplasias Pulmonares , Sequenciamento por Nanoporos , Humanos , Ácidos Nucleicos Livres/genética , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/genética , Genômica/métodos , Análise de Sequência de DNA , DNA/genética , Biomarcadores Tumorais/genéticaRESUMO
Aim: DNA methylation testing for endometrial cancer detection in minimally invasive specimens is a promising tool to improve screening and diagnostic procedures. Available literature was systematically reviewed to assess the potential of this approach and define methylation markers deserving further development. Methods: A systematic search up to March 31 2020 was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Results: 15 methylation markers with an area under the curve value of ≥ 0.80 for endometrial cancer detection in cytological specimens were selected from nine studies. Conclusion: Detection of methylation markers in cytological samples indicate the feasibility of minimally invasive testing methods, potentially guiding diagnosis and detection of endometrial cancer in high-risk women and in cancer screening programs.