Liquid Biopsies: Genotyping Circulating Tumor DNA
Open accessAbstract
Genotyping tumor tissue in search of somatic genetic alterations for actionable information has become routine practice in clinical oncology. Although these sequence alterations are highly informative, sampling tumor tissue has significant inherent limitations; tumor tissue is a single snapshot in time, is subject to selection bias resulting from tumor heterogeneity, and can be difficult to obtain. Cell-free fragments of DNA are shed into the bloodstream by cells undergoing apoptosis or necrosis, and the load of circulating cell-free DNA (cfDNA) correlates with tumor staging and prognosis. Moreover, recent advances in the sensitivity and accuracy of DNA analysis have allowed for genotyping of cfDNA for somatic genomic alterations found in tumors. The ability to detect and quantify tumor mutations has proven effective in tracking tumor dynamics in real time as well as serving as a liquid biopsy that can be used for a variety of clinical and investigational applications not previously possible.
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ctDNA analysis can offer a high degree of sensitivity and specificity to monitor the emergence of drug resistance during treatment.
“Such limitations could be overcome by less-invasive analysis of circulating tumor DNA, which can offer a high degree of sensitivity and specificity to monitor the emergence of drug resistance during the course of treatment [41, 135].”
From Primary and acquired resistance to EGFR-targeted therapies in colorectal cancer: impact on future treatment strategies (2014) · cites this paper as [135]
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- Authors
- Diaz, L. A., & Bardelli, A.
- Affiliations
- Johns Hopkins University (US)
- Venue
- Journal of Clinical Oncology
- Published
- 2014-02-20
- Volume
- 32
- Issue
- 6
- Pages
- 579-586
- ISSN
- 0732-183X (ISSN-L)
- 1527-7755
- PMC
- PMC4820760
- OpenAlex
- W2027735722
- Cited by
- 2,210
- References
- 87
- Citations by year
- 2026: 84 · 2025: 130 · 2024: 134 · 2023: 175 · 2022: 165 · 2021: 207 · 2020: 241 · 2019: 234 · 2018: 244 · 2017: 235 · 2016: 185 · 2015: 130 · 2014: 43 · 2013: 2
- FWCI
- 63.32
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Journal of Clinical Oncology (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Institutional Research Information System University of Turin (University of Turin) (submittedVersion)
- Funders
- National Cancer Institute (P30CA006973)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer Genomics and Diagnostics
- Health Sciences › Medicine › Pediatrics, Perinatology and Child Health › Prenatal Screening and Diagnostics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › BRCA gene mutations in cancer
- Keywords
- liquid biopsy, circulating tumor DNA, cell-free DNA, somatic mutations, tumor heterogeneity, tumor genotyping, actionable mutations, tumor staging, prognosis
- MeSH terms
- Biopsy, DNA, Neoplasm, Genotype, Humans, Neoplasms
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