Leveraging the Fragment Length of Circulating Tumour DNA to Improve Molecular Profiling of Solid Tumour Malignancies with Next-Generation Sequencing: A Pathway to Advanced Non-invasive Diagnostics in Precision Oncology?
Autor: | Hunter R. Underhill |
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Rok vydání: | 2021 |
Předmět: |
0301 basic medicine
In silico Computational biology medicine.disease_cause Malignancy Sensitivity and Specificity Article DNA sequencing Circulating Tumor DNA 03 medical and health sciences 0302 clinical medicine Gene Frequency Neoplasms Genetics Humans Medicine Precision Medicine Allele frequency Early Detection of Cancer Pharmacology Profiling (computer programming) Mutation business.industry High-Throughput Nucleotide Sequencing Sequence Analysis DNA General Medicine medicine.disease Molecular medicine Human genetics 030104 developmental biology 030220 oncology & carcinogenesis Molecular Medicine business |
Zdroj: | Mol Diagn Ther |
ISSN: | 1179-2000 1177-1062 |
Popis: | Circulating cell-free DNA (ccfDNA) has emerged as a promising diagnostic tool in oncology. Identification of tumour-derived ccfDNA (i.e. circulating tumour DNA [ctDNA]) provides non-invasive access to a malignancy's molecular landscape to diagnose, inform therapeutic strategies, and monitor treatment efficacy. Current applications of ccfDNA to detect somatic mutations, however, have been largely constrained to tumour-informed searches and identification of common mutations because of the interaction between ctDNA signal and next-generation sequencing (NGS) noise. Specifically, the low allele frequency of ctDNA associated with non-metastatic and early-stage lesions may be indistinguishable from artifacts that accrue during sample preparation and NGS. Thus, using ccfDNA to achieve non-invasive and personalized molecular profiling to optimize individual patient care is a highly sought goal that remains limited in clinical practice. There is growing evidence, however, that further advances in the field of ccfDNA diagnostics may be achieved by improving detection of somatic mutations through leveraging the inherently shorter fragment lengths of ctDNA compared to non-neoplastic ccfDNA. Here, the origins and rationale for seeking to improve the mutation-based detection of ctDNA by using ccfDNA size profiling are reviewed. Subsequently, in vitro and in silico methods to enrich for a target ccfDNA fragment length are detailed to identify current practices and provide perspective into the potential of using ccfDNA size profiling to impact clinical applications in oncology. |
Databáze: | OpenAIRE |
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