The DOI matches its Crossref record; 42 of the 42 references it cites were found in a registry or an index.
Ultra-sensitive detection of the pretreatment EGFR T790M mutation in non-small cell lung cancer patients with an EGFR-activating mutation using droplet digital PCR
Published version of a preprint
Abstract
PURPOSE: The resistance to the EGFR tyrosine kinase inhibitors (TKI) is a major concern in non-small cell lung cancer (NSCLC) treatment. T790M mutation in EGFR accounts for nearly 50% of the acquired resistance to EGFR-TKIs. Earlier studies suggested that T790M mutation was also detected in TKI-naïve NSCLCs in a small cohort. Here, we use an ultra-sensitive droplet digital PCR (ddPCR) technique to address the incidence and clinical significance of pretreatment T790M in a larger cohort. EXPERIMENTAL DESIGN: ddPCR was established as follows: wild-type or T790M mutation-containing DNA fragments were cloned into plasmids. Candidate threshold was identified using wild-type plasmid, normal human genomic DNA, and human A549 cell line DNA, which expresses wild type. Surgically resected tumor tissues from 373 NSCLC patients with EGFR-activating mutations were then examined for the presence of T790M using ddPCR. RESULTS: Our data revealed a linear performance for this ddPCR method (R(2) = 0.998) with an analytical sensitivity of approximately 0.001%. The overall incidence of the pretreatment T790M mutation was 79.9% (298/373), and the frequency ranged from 0.009% to 26.9%. The T790M mutation was detected more frequently in patients with a larger tumor size (P = 0.019) and those with common EGFR-activating mutations (P = 0.022), as compared with the others. CONCLUSIONS: The ultra-sensitive ddPCR assay revealed that pretreatment T790M was found in the majority of NSCLC patients with EGFR-activating mutations. ddPCR should be utilized for detailed assessment of the impact of the low frequency pretreatment T790M mutation on treatment with EGFR-TKIs.
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“determination of pretreatment T790M mutation status in formalin-fixed, paraffinembedded tissue by using standard sequencing platforms has been classically described in less than 5% of treatment-naïve tumors (Table 5)”
In the citing paper
“but with more sensitive techniques (e.g., droplet digital PCR), T790M can be detected in up to 80% of these tumors.34,37”
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Matsumoto, Y., Kawaguchi, T., Watanabe, M., 伊佐, 俊., Ando, M., Tamiya, A., Kubo, A., Kitagawa, C., Yoshimoto, N., & Koh, Y. (2022) · Figshare · doi:10.6084/m9.figshare.20329285
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Metadata
- Authors
- Watanabe, M., Kawaguchi, T., Isa, S.-I., Ando, M., Tamiya, A., Kubo, A., Saka, H., Takeo, S., Adachi, H., Tagawa, T., Kakegawa, S., Yamashita, M., Kataoka, K., Ichinose, Y., Takeuchi, Y., Sakamoto, K., Matsumura, A., & Koh, Y.
- Affiliations
- Wakayama Medical University (JP)
- Osaka City University (JP)
- NHO Kinki Chuo Chest Medical Center (JP)
- Nagoya University Hospital (JP)
- Aichi Medical University (JP)
- National Hospital Organization (JP)
- National Kyushu Medical Center (JP)
- Sapporo National Hospital (JP)
- Nagasaki Medical Center (JP)
- Shikoku Cancer Center (JP)
- Iwakuni Medical Center (JP)
- National Hospital Organization Kyushu Cancer Center (JP)
- Toneyama National Hospital (JP)
- National Hospital Organization Yokohama Medical Center (JP)
- Corresponding author
- Koh, Yasuhiro
- ORCID
- Venue
- Clinical Cancer Research
- Published
- 2015-08-01
- Volume
- 21
- Issue
- 15
- Pages
- 3552-3560
- ISSN
- 1078-0432 (ISSN-L)
- 1557-3265
- OpenAlex
- W2006126363
- Cited by
- 216
- References
- 42
- Citations by year
- 2026: 1 · 2025: 4 · 2024: 3 · 2023: 9 · 2022: 24 · 2021: 19 · 2020: 22 · 2019: 30 · 2018: 19 · 2017: 47 · 2016: 32 · 2015: 6
- FWCI
- 27.38
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Clinical Cancer Research (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Japan Society for the Promotion of Science (25460896, 23501314)
- Topics
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Lung Cancer Treatments and Mutations
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer Genomics and Diagnostics
- Health Sciences › Medicine › Oncology › HER2/EGFR in Cancer Research
- Keywords
- T790M mutation, non-small cell lung cancer, EGFR activating mutations, droplet digital PCR, EGFR tyrosine kinase inhibitors, acquired drug resistance, tumor size, analytical sensitivity
- MeSH terms
- Adult, Aged, Aged, 80 and over, Carcinoma, Non-Small-Cell Lung, Female, Gene Frequency, Humans, Male, Middle Aged, Mutation, Polymerase Chain Reaction, Drug Resistance, Neoplasm, Protein Kinase Inhibitors, Precision Medicine, ErbB Receptors
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