Ju Seok Kim1, Go Eun Bae2, Seok-Hwan Kim3, Min Kyung Choi2, Min-Kyung Yeo2. 1. Department of Internal Medicine, Chungnam National University School of Medicine, Daejeon, South Korea. 2. Department of Pathology, Chungnam National University School of Medicine, Daejeon, South Korea. 3. Department of Surgery, Chungnam National University School of Medicine, Daejeon, South Korea.
Abstract
BACKGROUND: Cell-free DNA (cfDNA) has arisen as an alternative target for evaluating somatic mutations in cancer. KRAS mutation status is critical for targeted therapy in colorectal adenocarcinoma (CRAC). We evaluated KRASG12/G13 mutations in cfDNA extracted from serum and compared the results with KRASG12/G13 mutations detected in tissue samples. We assessed the clinical significance of KRASG12/G13 mutation in serum in regard to recurrence and metastasis of CRAC. METHODS: A total of 146 CRAC patients were enrolled, and KRASG12/G13 mutations were evaluated in 146 pairs of serum and tissue samples. In addition, 35 pairs of primary and metastatic CRAC tissue samples were evaluated for KRASG12/G13 mutational status. RESULTS: Detection of KRASG12/13 mutation from serum and tissue had a 55% concordance rate, and serum detection had a sensitivity of 39.8%. Detection of the KRASG12/13 mutation yielded a 14% discordance rate between primary and metastatic tissue. CRAC patients with mutant KRASG12/13 mutation in serum but wild-type KRASG12/13 in tissue had concurrent KRASG12/13-mutant metastatic tumors, indicating spatial genetic heterogeneity. Changes in serum KRASG12/G13 mutation status during postoperative follow-up were associated with recurrence. Conclusion: Although serum detection of the KRASG12/13 mutation cannot substitute for detection in tissue, serum testing can support the interpretation of a CRAC patient's status in regard to concurrent metastasis. Dynamic changes in serum KRASG12/13 mutation status during follow-up indicated that cfDNA from serum represents a potential source for monitoring recurrence in CRAC patients.
BACKGROUND: Cell-free DNA (cfDNA) has arisen as an alternative target for evaluating somatic mutations in cancer. KRAS mutation status is critical for targeted therapy in colorectal adenocarcinoma (CRAC). We evaluated KRASG12/G13 mutations in cfDNA extracted from serum and compared the results with KRASG12/G13 mutations detected in tissue samples. We assessed the clinical significance of KRASG12/G13 mutation in serum in regard to recurrence and metastasis of CRAC. METHODS: A total of 146 CRAC patients were enrolled, and KRASG12/G13 mutations were evaluated in 146 pairs of serum and tissue samples. In addition, 35 pairs of primary and metastatic CRAC tissue samples were evaluated for KRASG12/G13 mutational status. RESULTS: Detection of KRASG12/13 mutation from serum and tissue had a 55% concordance rate, and serum detection had a sensitivity of 39.8%. Detection of the KRASG12/13 mutation yielded a 14% discordance rate between primary and metastatic tissue. CRAC patients with mutant KRASG12/13 mutation in serum but wild-type KRASG12/13 in tissue had concurrent KRASG12/13-mutant metastatic tumors, indicating spatial genetic heterogeneity. Changes in serum KRASG12/G13 mutation status during postoperative follow-up were associated with recurrence. Conclusion: Although serum detection of the KRASG12/13 mutation cannot substitute for detection in tissue, serum testing can support the interpretation of a CRAC patient's status in regard to concurrent metastasis. Dynamic changes in serum KRASG12/13 mutation status during follow-up indicated that cfDNA from serum represents a potential source for monitoring recurrence in CRAC patients.
Authors: Miguel Alcaide; Matthew Cheung; Kevin Bushell; Sarah E Arthur; Hui-Li Wong; Joanna Karasinska; Daniel Renouf; David F Schaeffer; Suzan McNamara; Mathilde Couetoux du Tertre; Gerald Batist; Hagen F Kennecke; Aly Karsan; Ryan D Morin Journal: J Mol Diagn Date: 2018-11-23 Impact factor: 5.568
Authors: Steven M Bray; Jeeyun Lee; Seung Tae Kim; Joon Young Hur; Philip J Ebert; John N Calley; Isabella H Wulur; Thejaswini Gopalappa; Swee Seong Wong; Hui-Rong Qian; Jason C Ting; Jiangang Liu; Melinda D Willard; Ruslan D Novosiadly; Young Suk Park; Joon Oh Park; Ho Yeong Lim; Won Ki Kang; Amit Aggarwal; Hee Cheol Kim; Christoph Reinhard Journal: Sci Rep Date: 2019-10-25 Impact factor: 4.379