Serum-Based KRASG12/G13 Mutation Detection Using Droplet Digital PCR: Clinical Implications and Limitations in Colorectal Adenocarcinoma With Tumor Heterogeneity

Ju Seok Kim; Go Eun Bae; Seok-Hwan Kim; Min Kyung Choi; Min-Kyung Yeo

doi:10.3389/fonc.2020.604772

Serum-Based KRAS^G12/G13 Mutation Detection Using Droplet Digital PCR: Clinical Implications and Limitations in Colorectal Adenocarcinoma With Tumor Heterogeneity

Front Oncol. 2021 Jan 11:10:604772. doi: 10.3389/fonc.2020.604772. eCollection 2020.

Authors

Ju Seok Kim¹, Go Eun Bae², Seok-Hwan Kim³, Min Kyung Choi², Min-Kyung Yeo²

Affiliations

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 KRAS^G12/G13 mutations in cfDNA extracted from serum and compared the results with KRAS^G12/G13 mutations detected in tissue samples. We assessed the clinical significance of KRAS^G12/G13 mutation in serum in regard to recurrence and metastasis of CRAC.

Methods: A total of 146 CRAC patients were enrolled, and KRAS^G12/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 KRAS^G12/G13 mutational status.

Results: Detection of KRAS^G12/13 mutation from serum and tissue had a 55% concordance rate, and serum detection had a sensitivity of 39.8%. Detection of the KRAS^G12/13 mutation yielded a 14% discordance rate between primary and metastatic tissue. CRAC patients with mutant KRAS^G12/13 mutation in serum but wild-type KRAS^G12/13 in tissue had concurrent KRAS^G12/13-mutant metastatic tumors, indicating spatial genetic heterogeneity. Changes in serum KRAS^G12/G13 mutation status during postoperative follow-up were associated with recurrence. Conclusion: Although serum detection of the KRAS^G12/13 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 KRAS^G12/13 mutation status during follow-up indicated that cfDNA from serum represents a potential source for monitoring recurrence in CRAC patients.

Keywords: KRAS; cell free DNA; colorectal adenocarcinoma; heterogeneity; serum.