Ultra-deep massively parallel sequencing with unique molecular identifier tagging achieves comparable performance to droplet digital PCR for detection and quantification of circulating tumor DNA from lung cancer patients.
The identification and quantification of actionable mutations are of critical importance for effective genotype-directed therapies, prognosis and drug response monitoring in patients with non-small-cell lung cancer (NSCLC). Although tumor tissue biopsy remains the gold standard for diagnosis of NSCL...
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Public Library of Science (PLoS)
2019-01-01
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| Online Access: | https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0226193&type=printable |
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| author | Le Son Tran Hong-Anh Thi Pham Vu-Uyen Tran Thanh-Truong Tran Anh-Thu Huynh Dang Dinh-Thong Le Son-Lam Nguyen Ngoc-Vu Nguyen Trieu-Vu Nguyen Binh Thanh Vo Hong-Thuy Thi Dao Nguyen Huu Nguyen Tam Huu Tran Chu Van Nguyen Phuong Cam Pham Anh Tuan Dang-Mai Thien Kim Dinh-Nguyen Van Hieu Phan Thanh-Thuy Thi Do Kiet Truong Dinh Han Ngoc Do Minh-Duy Phan Hoa Giang Hoai-Nghia Nguyen |
| author_facet | Le Son Tran Hong-Anh Thi Pham Vu-Uyen Tran Thanh-Truong Tran Anh-Thu Huynh Dang Dinh-Thong Le Son-Lam Nguyen Ngoc-Vu Nguyen Trieu-Vu Nguyen Binh Thanh Vo Hong-Thuy Thi Dao Nguyen Huu Nguyen Tam Huu Tran Chu Van Nguyen Phuong Cam Pham Anh Tuan Dang-Mai Thien Kim Dinh-Nguyen Van Hieu Phan Thanh-Thuy Thi Do Kiet Truong Dinh Han Ngoc Do Minh-Duy Phan Hoa Giang Hoai-Nghia Nguyen |
| author_sort | Le Son Tran |
| collection | DOAJ |
| description | The identification and quantification of actionable mutations are of critical importance for effective genotype-directed therapies, prognosis and drug response monitoring in patients with non-small-cell lung cancer (NSCLC). Although tumor tissue biopsy remains the gold standard for diagnosis of NSCLC, the analysis of circulating tumor DNA (ctDNA) in plasma, known as liquid biopsy, has recently emerged as an alternative and noninvasive approach for exploring tumor genetic constitution. In this study, we developed a protocol for liquid biopsy using ultra-deep massively parallel sequencing (MPS) with unique molecular identifier tagging and evaluated its performance for the identification and quantification of tumor-derived mutations from plasma of patients with advanced NSCLC. Paired plasma and tumor tissue samples were used to evaluate mutation profiles detected by ultra-deep MPS, which showed 87.5% concordance. Cross-platform comparison with droplet digital PCR demonstrated comparable detection performance (91.4% concordance, Cohen's kappa coefficient of 0.85 with 95% CI = 0.72-0.97) and great reliability in quantification of mutation allele frequency (Intraclass correlation coefficient of 0.96 with 95% CI = 0.90-0.98). Our results highlight the potential application of liquid biopsy using ultra-deep MPS as a routine assay in clinical practice for both detection and quantification of actionable mutation landscape in NSCLC patients. |
| format | Article |
| id | doaj-art-d2c70cc813ba446987362f652e3f3ffe |
| institution | DOAJ |
| issn | 1932-6203 |
| language | English |
| publishDate | 2019-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj-art-d2c70cc813ba446987362f652e3f3ffe2025-08-20T02:55:14ZengPublic Library of Science (PLoS)PLoS ONE1932-62032019-01-011412e022619310.1371/journal.pone.0226193Ultra-deep massively parallel sequencing with unique molecular identifier tagging achieves comparable performance to droplet digital PCR for detection and quantification of circulating tumor DNA from lung cancer patients.Le Son TranHong-Anh Thi PhamVu-Uyen TranThanh-Truong TranAnh-Thu Huynh DangDinh-Thong LeSon-Lam NguyenNgoc-Vu NguyenTrieu-Vu NguyenBinh Thanh VoHong-Thuy Thi DaoNguyen Huu NguyenTam Huu TranChu Van NguyenPhuong Cam PhamAnh Tuan Dang-MaiThien Kim Dinh-NguyenVan Hieu PhanThanh-Thuy Thi DoKiet Truong DinhHan Ngoc DoMinh-Duy PhanHoa GiangHoai-Nghia NguyenThe identification and quantification of actionable mutations are of critical importance for effective genotype-directed therapies, prognosis and drug response monitoring in patients with non-small-cell lung cancer (NSCLC). Although tumor tissue biopsy remains the gold standard for diagnosis of NSCLC, the analysis of circulating tumor DNA (ctDNA) in plasma, known as liquid biopsy, has recently emerged as an alternative and noninvasive approach for exploring tumor genetic constitution. In this study, we developed a protocol for liquid biopsy using ultra-deep massively parallel sequencing (MPS) with unique molecular identifier tagging and evaluated its performance for the identification and quantification of tumor-derived mutations from plasma of patients with advanced NSCLC. Paired plasma and tumor tissue samples were used to evaluate mutation profiles detected by ultra-deep MPS, which showed 87.5% concordance. Cross-platform comparison with droplet digital PCR demonstrated comparable detection performance (91.4% concordance, Cohen's kappa coefficient of 0.85 with 95% CI = 0.72-0.97) and great reliability in quantification of mutation allele frequency (Intraclass correlation coefficient of 0.96 with 95% CI = 0.90-0.98). Our results highlight the potential application of liquid biopsy using ultra-deep MPS as a routine assay in clinical practice for both detection and quantification of actionable mutation landscape in NSCLC patients.https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0226193&type=printable |
| spellingShingle | Le Son Tran Hong-Anh Thi Pham Vu-Uyen Tran Thanh-Truong Tran Anh-Thu Huynh Dang Dinh-Thong Le Son-Lam Nguyen Ngoc-Vu Nguyen Trieu-Vu Nguyen Binh Thanh Vo Hong-Thuy Thi Dao Nguyen Huu Nguyen Tam Huu Tran Chu Van Nguyen Phuong Cam Pham Anh Tuan Dang-Mai Thien Kim Dinh-Nguyen Van Hieu Phan Thanh-Thuy Thi Do Kiet Truong Dinh Han Ngoc Do Minh-Duy Phan Hoa Giang Hoai-Nghia Nguyen Ultra-deep massively parallel sequencing with unique molecular identifier tagging achieves comparable performance to droplet digital PCR for detection and quantification of circulating tumor DNA from lung cancer patients. PLoS ONE |
| title | Ultra-deep massively parallel sequencing with unique molecular identifier tagging achieves comparable performance to droplet digital PCR for detection and quantification of circulating tumor DNA from lung cancer patients. |
| title_full | Ultra-deep massively parallel sequencing with unique molecular identifier tagging achieves comparable performance to droplet digital PCR for detection and quantification of circulating tumor DNA from lung cancer patients. |
| title_fullStr | Ultra-deep massively parallel sequencing with unique molecular identifier tagging achieves comparable performance to droplet digital PCR for detection and quantification of circulating tumor DNA from lung cancer patients. |
| title_full_unstemmed | Ultra-deep massively parallel sequencing with unique molecular identifier tagging achieves comparable performance to droplet digital PCR for detection and quantification of circulating tumor DNA from lung cancer patients. |
| title_short | Ultra-deep massively parallel sequencing with unique molecular identifier tagging achieves comparable performance to droplet digital PCR for detection and quantification of circulating tumor DNA from lung cancer patients. |
| title_sort | ultra deep massively parallel sequencing with unique molecular identifier tagging achieves comparable performance to droplet digital pcr for detection and quantification of circulating tumor dna from lung cancer patients |
| url | https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0226193&type=printable |
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