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High-sensitivity assay for monitoring ESR1 mutations in circulating cell-free DNA of breast cancer patients receiving endocrine therapy
- Source :
- Scientific Reports, Scientific Reports, Vol 8, Iss 1, Pp 1-10 (2018)
- Publication Year :
- 2018
-
Abstract
- Approximately 70% of breast cancers (BCs) express estrogen receptor alpha (ERα) and are treated with endocrine therapy. However, the effectiveness of this therapy is limited by innate or acquired resistance in approximately one-third of patients. Activating mutations in the ESR1 gene that encodes ERα promote critical resistance mechanisms. Here, we developed a high sensitivity approach based on enhanced-ice-COLD-PCR for detecting ESR1 mutations. The method produced an enrichment up to 100-fold and allowed the unambiguous detection of ESR1 mutations even when they consisted of only 0.01% of the total ESR1 allelic fraction. After COLD-PCR enrichment, methods based on next-generation sequencing or droplet-digital PCR were employed to detect and quantify ESR1 mutations. We applied the method to detect ESR1 mutations in circulating free DNA from the plasma of 56 patients with metastatic ER-positive BC. Fifteen of these patients were found to have ESR1 mutations at codons 536–538. This study demonstrates the utility of the enhanced-ice-COLD-PCR approach for simplifying and improving the detection of ESR1 tumor mutations in liquid biopsies. Because of its high sensitivity, the approach may potentially be applicable to patients with non-metastatic disease.
- Subjects :
- 0301 basic medicine
lcsh:Medicine
Socio-culturale
Breast Neoplasms
Disease
Endocrine Disruptors
Polymerase Chain Reaction
Article
Liquid biopsies
03 medical and health sciences
chemistry.chemical_compound
0302 clinical medicine
Breast cancer
Neoplasms
Medicine
Humans
Allele
Neoplasm Metastasis
lcsh:Science
Codon
Gene
Multidisciplinary
business.industry
lcsh:R
Endocrine therapy
Estrogen Receptor alpha
Liquid Biopsy
DNA
medicine.disease
Circulating Cell-Free DNA
body regions
030104 developmental biology
chemistry
030220 oncology & carcinogenesis
Mutation
Cancer research
lcsh:Q
Female
business
Estrogen receptor alpha
Cell-Free Nucleic Acids
Subjects
Details
- Language :
- English
- Database :
- OpenAIRE
- Journal :
- Scientific Reports, Scientific Reports, Vol 8, Iss 1, Pp 1-10 (2018)
- Accession number :
- edsair.doi.dedup.....66053e972b6aee7508a610e2a63c7c32