Extending Circulating Tumor DNA Analysis to Ultralow Abundance Mutations: Techniques and Challenges
| Autor: | Simon R. Corrie, Bradyn J. Parker, Andrew Spencer, Andrew Edwin Rodda |
|---|---|
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Fluid Flow and Transfer Processes Base pair Process Chemistry and Technology Liquid Biopsy Bioengineering Computational biology Biology Circulating Tumor DNA 03 medical and health sciences 030104 developmental biology 0302 clinical medicine Cell-free fetal DNA Circulating tumor DNA 030220 oncology & carcinogenesis Mutation Biomarkers Tumor Humans Multiplex Liquid biopsy Instrumentation Clinical treatment Volume concentration |
| Zdroj: | ACS Sensors. 3:540-560 |
| ISSN: | 2379-3694 |
| DOI: | 10.1021/acssensors.7b00953 |
| Popis: | Liquid biopsies that analyze circulating tumor DNA (ctDNA) hold great promise in the guidance of clinical treatment for various cancers. However, the innate characteristics of ctDNA make it a difficult target: ctDNA is highly fragmented, and found at very low concentrations, both in absolute terms and relative to wildtype species. Clinically relevant target sequences often differ from the wildtype species by a single DNA base pair. These characteristics make analyzing mutant ctDNA a uniquely difficult process. Despite this, techniques have recently emerged for analyzing ctDNA, and have been used in pilot studies that showed promising results. These techniques each have various drawbacks, either in their analytical capabilities or in practical considerations, which restrict their application to many clinical situations. Many of the most promising potential applications of ctDNA require assay characteristics that are not currently available, and new techniques with these properties could have benefits in companion diagnostics, monitoring response to treatment and early detection. Here we review the current state of the art in ctDNA detection, with critical comparison of the analytical techniques themselves. We also examine the improvements required to expand ctDNA diagnostics to more advanced applications and discuss the most likely pathways for these improvements. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|