Abstract
KRAS mutations are responsible for resistance to anti-epidermal growth factor receptor (EGFR) therapy in colorectal cancer patients. These mutations sometimes appear once treatment has started. Detection of KRAS mutations in circulating cell-free DNA in plasma (“liquid biopsy”) by droplet digital PCR (ddPCR) has emerged as a very sensitive and promising alternative to serial biopsies for disease monitoring. In this study, KRAS G12V mutation was analyzed by ddPCR in plasma DNA from 10 colorectal cancer patients and compared to six healthy donors. The percentage of KRAS G12V mutation relative to wild-type sequences in tumor-derived DNA was also determined. KRAS G12V mutation circulating in plasma was detected in 9 of 10 colorectal cancer patients whose tumors were also mutated. Colorectal cancer patients had 35.62 copies of mutated KRAS/mL plasma, whereas in healthy controls only residual copies were found (0.62 copies/mL, p = 0.0066). Interestingly, patients with metastatic disease showed a significantly higher number of mutant copies than M0 patients (126.25 versus 9.37 copies/mL, p = 0.0286). Wild-type KRAS was also significantly elevated in colorectal cancer patients compared to healthy controls (7718.8 versus 481.25 copies/mL, p = 0.0002). In conclusion, KRAS G12V mutation is detectable in plasma of colorectal cancer patients by ddPCR and could be used as a non-invasive biomarker.
Highlights
In the past few years, cancer treatment has evolved markedly towards more personalized targeted therapies
Only patients with KRAS wild-type tumors can benefit from anti-epidermal growth factor receptor (EGFR) therapies, since it has been demonstrated that KRAS mutations predispose to drug resistance [1]
DNA fragments released by tumor cells, which can be found circulating in plasma and are termed as circulating tumor DNA, have given rise to the concept of “liquid biopsy” [2]
Summary
In the past few years, cancer treatment has evolved markedly towards more personalized targeted therapies. We should be able to overcome these issues and rapidly identify biomarkers in a cost-effective and non-invasive manner to monitor treatment response at different time points during the course of disease. To this end, DNA fragments released by tumor cells, which can be found circulating in plasma and are termed as circulating tumor DNA (ctDNA), have given rise to the concept of “liquid biopsy” [2]. The main problem impeding more widespread use of liquid biopsy is that certain clinical scenarios exist, at early stages of disease, where levels of circulating tumor DNA are below the limits of detection of currently applied techniques [3]
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