Oncotarget. 2018 May 11;9(36):24398-24413. doi: 10.18632/oncotarget.25309. eCollection 2018 May 11.
Monitoring circulating tumor DNA revealed dynamic changes in KRAS status in patients with metastatic colorectal cancer.
Takayama Y1, Suzuki K1, Muto Y1, Ichida K1, Fukui T1, Kakizawa N1, Ishikawa H1, Watanabe F1, Hasegawa F1, Saito M1, Tsujinaka S1, Futsuhara K1, Miyakura Y1, Noda H1, Konishi F2, Rikiyama T1.
KRAS mutated circulating tumor DNA (MctDNA) can be monitored in the blood of patients with metastatic colorectal cancer (mCRC), but dynamic changes have not been determined. Four hundred and fifty-seven plasma samples were collected prospectively from 85 mCRC patients who underwent chemotherapy. MctDNA in plasma was detected by droplet digital PCR, and the percentage of MctDNA in total circulating cell-free DNA was calculated. KRAS assessment in tumor tissues showed 29 patients with the mutant-type (MT) and 56 patients with the wild-type (WT). Twenty-three of 29 MT patients (79.3%) and 28 of 56 WT patients (50.0%) showed MctDNA. Emergence of MctDNA was recognized during treatments with various drugs. Regardless of KRAS status in tumor tissues, patients with MctDNA in blood showed poor progression-free survival with first-line treatment. Median percentage of MctDNA accounted for 10.10% in MT patients and 0.22% in WT patients. These differences between MT and WT likely affected patterns of changes in MctDNA. KRAS monitoring identified dynamic changes in MctDNA, such as continuous, intermittent, and transient changes (quick elevation and disappearance). Emergence of MctDNA involved drug resistance, except for transient changes, which were seen in WT patients and likely corresponded with the drug response. Transient changes could be involved in recovery of sensitivity to anti-EGFR antibody in WT patients. Monitoring MctDNA during various treatments showed dynamic changes in KRAS status and could provide useful information for determining treatments for patients with mCRC.
KRAS; circulating tumor DNA; colorectal cancer; droplet digital PCR; liquid biopsy