KRAS G12V mutation detection by droplet digital PCR in circulating cell-free DNA of colorectal cancer patients
EntityUAM. Departamento de Cirugía; Instituto de Investigación Sanitaria Fundación Jiménez Díaz (IIS-FJD)
10.3390/ijms17040484International Journal of Molecular Sciences 17.4 (2016): 1-9
ISSN1661-6596 (print); 1422-0067 (online)
Funded byThis study was funded by a grant from “Fondo de Investigaciones Sanitarias-FEDER”, Ministry of Health, Spain (FIS; PI13/01924) and the Spanish Ministry of Health and Consumer Affairs (via a cooperative network-FEDER [TerCel RD12- 0019-0035])
SubjectsCirculating cell-free DNA; Colorectal cancer; Droplet digital PCR; KRAS; Plasma; Medicina
Rights© 2016 by the authors
Esta obra está bajo una Licencia Creative Commons Atribución 4.0 Internacional.
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.
Google Scholar:Olmedillas López, Susana - García-Olmo, Dolores C. - García Arranz, Mariano Andrés - Guadalajara Labajo, Héctor - Pastor, Carlos - García Olmo, Damián
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