Quantitative Detection of EGFR Mutations in Circulating Tumor DNA Derived from Lung Adenocarcinomas
Published version of a preprint
Abstract
PURPOSE: Examination of somatic epidermal growth factor receptor (EGFR) mutations is now a diagnostic routine for treatment of cancer using EGFR tyrosine kinase inhibitors (EGFR-TKI). Circulating tumor DNA is a promising target for noninvasive diagnostics. We evaluated its utility by quantitatively detecting activating and resistant mutations, which were measured with BEAMing (beads, emulsion, amplification, and magnetics). EXPERIMENTAL DESIGN: Twenty-three patients with lung cancer with progressive disease after EGFR-TKI treatment and 21 patients who had never been treated with EGFR-TKIs were studied. Their primary tumors were confirmed to have activating mutations. In the plasma DNA of each patient, the activating mutation found in the corresponding primary tumor and the T790M resistance mutation were quantified by BEAMing. RESULTS: In 32 of 44 patients, activating mutations were detected in the plasma DNA [72.7%; 95% confidence interval (CI), 58.0%-83.6%]. The T790M mutation was detected in 10 of 23 patients in the first group (43.5%; 95% CI, 25.6%-53.4%). The ratio of T790M to activating mutations ranged from 13.3% to 94.0%. The peak of the distribution of the mutation allele fraction in the plasma DNA was in the 0.1% to 1% range. CONCLUSIONS: The major advantage of BEAMing is its ability to calculate the fraction of T790M-positive alleles from the alleles with activating mutations. This feature enables the detection of increases and decreases in the number of T790M mutations in cancer cells, regardless of normal cell DNA contamination, which may be useful for monitoring disease progression. Circulating tumor DNA could potentially be used as an alternative method for EGFR mutation detection.
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Preclinical data confirmed that P110α E545K, a PIK3CA oncogenic mutation, resulted in dramatically suppressed sensitivity to gefitinib.
“Preclinical data confirmed that P110α E545K, a PIK3CA oncogenic mutation, resulted in dramatically suppressed sensitivity to gefitinib.53”
From Mechanisms of resistance to EGFR-targeted drugs: lung cancer (2016) · cites this paper as [53]
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- Authors
- Taniguchi, K., Uchida, J., Nishino, K., Kumagai, T., Okuyama, T., Okami, J., Higashiyama, M., Kodama, K., Imamura, F., & Kato, K.
- Affiliations
- Osaka International Cancer Institute (JP)
- Venue
- Clinical Cancer Research
- Published
- 2011-12-15
- Volume
- 17
- Issue
- 24
- Pages
- 7808-7815
- ISSN
- 1078-0432 (ISSN-L)
- 1557-3265
- OpenAlex
- W2107503225
- Cited by
- 315
- References
- 30
- Citations by year
- 2026: 2 · 2025: 5 · 2024: 3 · 2023: 6 · 2022: 8 · 2021: 18 · 2020: 21 · 2019: 23 · 2018: 32 · 2017: 35 · 2016: 52 · 2015: 47 · 2014: 28 · 2013: 24 · 2012: 9
- FWCI
- 6.80
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Clinical Cancer Research (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Japan Society for the Promotion of Science (23790636)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer Genomics and Diagnostics
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Lung Cancer Treatments and Mutations
- Health Sciences › Medicine › Oncology › HER2/EGFR in Cancer Research
- Keywords
- EGFR mutation, circulating tumor DNA, lung adenocarcinoma, T790M mutation, EGFR tyrosine kinase inhibitors, beaming, liquid biopsy, non-invasive cancer diagnosis, disease progression monitoring
- MeSH terms
- Adenocarcinoma, Adult, Aged, Aged, 80 and over, DNA Mutational Analysis, DNA, Neoplasm, Female, Gene Frequency, Humans, Lung Neoplasms, Male, Middle Aged, Mutation, Sensitivity and Specificity, Reproducibility of Results, Amino Acid Substitution, Young Adult, ErbB Receptors
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