Evaluation of a Liquid Biopsy Protocol using Ultra-Deep Massive Parallel Sequencing for Detecting and Quantifying Circulation Tumor DNA in Colorectal Cancer Patients

• Published in: Cancer investigation 2020-02, Vol.38 (2), p.85-93
• Main Authors: Nguyen, Huu Thinh, Tran, Duc Huy, Ngo, Quoc Dat, Pham, Hong-Anh Thi, Tran, Thanh-Truong, Tran, Vu-Uyen, Pham, Truong-Vinh Ngoc, Le, Trung Kien, Le, Ngoc-An Trinh, Nguyen, Ngoc Mai, Vo, Binh Thanh, Nguyen, Luan Thanh, Nguyen, Thien-Chi Van, Bui, Quynh Tram Nguyen, Nguyen, Huu-Nguyen, Luong, Bac An, Le, Linh Gia Hoang, Do, Duc Minh, Do, Thanh-Thuy Thi, Hoang, Anh Vu, Dinh, Kiet Truong, Phan, Minh-Duy, Tran, Le Son, Giang, Hoa, Nguyen, Hoai-Nghia
• Format: Article
• Language: English
• Subjects: actionable mutation; circulating tumor DNA; Circulating Tumor DNA - genetics; colorectal cancer; Colorectal Neoplasms - blood; Colorectal Neoplasms - genetics; GTP Phosphohydrolases - genetics; High-Throughput Nucleotide Sequencing - methods; Humans; Liquid biopsy; Liquid Biopsy - methods; Membrane Proteins - genetics; Mutation; Proto-Oncogene Proteins B-raf - genetics; Proto-Oncogene Proteins p21(ras) - genetics; Reproducibility of Results; ultra-deep sequencing
• ISSN: 0735-7907; 1532-4192
• DOI: 10.1080/07357907.2020.1713350

The identification and quantification of actionable mutations are critical for guiding targeted therapy and monitoring drug response in colorectal cancer. Liquid biopsy (LB) based on plasma cell-free DNA analysis has emerged as a noninvasive approach with many clinical advantages over conventional tissue sampling. Here, we developed a LB protocol using ultra-deep massive parallel sequencing and validated its clinical performance for detection and quantification of actionable mutations in three major driver genes (KRAS, NRAS and BRAF). The assay showed a 92% concordance for mutation detection between plasma and paired tissues and great reliability in quantification of variant allele frequency.