KRAS G12V mutation detection by droplet digital PCR in circulating cell-free DNA of colorectal cancer patients

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 PC...

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Detalles Bibliográficos
Autores: Olmedillas López, Susana, García-Olmo, Dolores C., García Arranz, Mariano Andrés, Guadalajara Labajo, Héctor, Pastor, Carlos, García Olmo, Damián
Tipo de recurso: artículo
Fecha de publicación:2016
País:España
Institución:Universidad Autónoma de Madrid
Repositorio:Biblos-e Archivo. Repositorio Institucional de la UAM
Idioma:inglés
OAI Identifier:oai:repositorio.uam.es:10486/677877
Acceso en línea:http://hdl.handle.net/10486/677877
https://dx.doi.org/10.3390/ijms17040484
Access Level:acceso abierto
Palabra clave:Circulating cell-free DNA
Colorectal cancer
Droplet digital PCR
KRAS
Plasma
Medicina
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spelling KRAS G12V mutation detection by droplet digital PCR in circulating cell-free DNA of colorectal cancer patientsOlmedillas López, SusanaGarcía-Olmo, Dolores C.García Arranz, Mariano AndrésGuadalajara Labajo, HéctorPastor, CarlosGarcía Olmo, DamiánCirculating cell-free DNAColorectal cancerDroplet digital PCRKRASPlasmaMedicinaKRAS 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.This 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])MDPIDepartamento de CirugíaFacultad de MedicinaInstituto de Investigación Sanitaria Fundación Jiménez Díaz (IIS-FJD)20162016-04-01research articlehttp://purl.org/coar/resource_type/c_2df8fbb1VoRhttp://purl.org/coar/version/c_970fb48d4fbd8a85info:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10486/677877https://dx.doi.org/10.3390/ijms17040484reponame:Biblos-e Archivo. Repositorio Institucional de la UAMinstname:Universidad Autónoma de MadridInglésengopen accesshttp://purl.org/coar/access_right/c_abf2info:eu-repo/semantics/openAccessoai:repositorio.uam.es:10486/6778772026-06-23T12:46:27Z
dc.title.none.fl_str_mv KRAS G12V mutation detection by droplet digital PCR in circulating cell-free DNA of colorectal cancer patients
title KRAS G12V mutation detection by droplet digital PCR in circulating cell-free DNA of colorectal cancer patients
spellingShingle KRAS G12V mutation detection by droplet digital PCR in circulating cell-free DNA of colorectal cancer patients
Olmedillas López, Susana
Circulating cell-free DNA
Colorectal cancer
Droplet digital PCR
KRAS
Plasma
Medicina
title_short KRAS G12V mutation detection by droplet digital PCR in circulating cell-free DNA of colorectal cancer patients
title_full KRAS G12V mutation detection by droplet digital PCR in circulating cell-free DNA of colorectal cancer patients
title_fullStr KRAS G12V mutation detection by droplet digital PCR in circulating cell-free DNA of colorectal cancer patients
title_full_unstemmed KRAS G12V mutation detection by droplet digital PCR in circulating cell-free DNA of colorectal cancer patients
title_sort KRAS G12V mutation detection by droplet digital PCR in circulating cell-free DNA of colorectal cancer patients
dc.creator.none.fl_str_mv Olmedillas López, Susana
García-Olmo, Dolores C.
García Arranz, Mariano Andrés
Guadalajara Labajo, Héctor
Pastor, Carlos
García Olmo, Damián
author Olmedillas López, Susana
author_facet Olmedillas López, Susana
García-Olmo, Dolores C.
García Arranz, Mariano Andrés
Guadalajara Labajo, Héctor
Pastor, Carlos
García Olmo, Damián
author_role author
author2 García-Olmo, Dolores C.
García Arranz, Mariano Andrés
Guadalajara Labajo, Héctor
Pastor, Carlos
García Olmo, Damián
author2_role author
author
author
author
author
dc.contributor.none.fl_str_mv Departamento de Cirugía
Facultad de Medicina
Instituto de Investigación Sanitaria Fundación Jiménez Díaz (IIS-FJD)
dc.subject.none.fl_str_mv Circulating cell-free DNA
Colorectal cancer
Droplet digital PCR
KRAS
Plasma
Medicina
topic Circulating cell-free DNA
Colorectal cancer
Droplet digital PCR
KRAS
Plasma
Medicina
description 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.
publishDate 2016
dc.date.none.fl_str_mv 2016
2016-04-01
dc.type.none.fl_str_mv research article
http://purl.org/coar/resource_type/c_2df8fbb1
VoR
http://purl.org/coar/version/c_970fb48d4fbd8a85
dc.type.openaire.fl_str_mv info:eu-repo/semantics/article
format article
dc.identifier.none.fl_str_mv http://hdl.handle.net/10486/677877
https://dx.doi.org/10.3390/ijms17040484
url http://hdl.handle.net/10486/677877
https://dx.doi.org/10.3390/ijms17040484
dc.language.none.fl_str_mv Inglés
eng
language_invalid_str_mv Inglés
language eng
dc.rights.none.fl_str_mv open access
http://purl.org/coar/access_right/c_abf2
dc.rights.openaire.fl_str_mv info:eu-repo/semantics/openAccess
rights_invalid_str_mv open access
http://purl.org/coar/access_right/c_abf2
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv MDPI
publisher.none.fl_str_mv MDPI
dc.source.none.fl_str_mv reponame:Biblos-e Archivo. Repositorio Institucional de la UAM
instname:Universidad Autónoma de Madrid
instname_str Universidad Autónoma de Madrid
reponame_str Biblos-e Archivo. Repositorio Institucional de la UAM
collection Biblos-e Archivo. Repositorio Institucional de la UAM
repository.name.fl_str_mv
repository.mail.fl_str_mv
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