Detection of KRAS Mutations in Plasma DNA Using a fully Automated Rapid Detection System in Colorectal Cancer Patients View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2017-10

AUTHORS

Kazuhisa Hosoya, Satoshi Matsusaka, Tomomi Kashiwada, Koichi Suzuki, Norio Ureshino, Akemi Sato, Yoshio Miki, Kazuki Kitera, Mitsuharu Hirai, Kiyohiko Hatake, Shinya Kimura, Naoko Sueoka-Aragane

ABSTRACT

KRAS mutations have been recognized as predictive markers of primary resistance to anti-EGFR-antibodies in colorectal cancer patients. In addition, newly detected KRAS mutations have been reported to be related with acquired resistance to chemotherapy containing anti-EGFR antibody. Considering this evidence, monitoring of KRAS mutations is indispensable for making treatment decisions, and the method should be non-invasive allowing repeated examinations. Recently, we established a novel automated sensitive detection system for KRAS mutations, named mutation-biased PCR quenching probe system (MBP-QP). The goal of our study was to investigate the potential for monitoring KRAS mutations during treatment with anti-EGFR antibodies. The detection limit of MBP-QP using a control plasmid containing KRAS mutations was 1-9 copies, and 0.05-0.3% mutant plasmid was detectable in a mixture of wild type and mutants. One-hundred twenty colorectal cancer patients were genotyped for KRAS mutations with MBP-QP as well as polymerase chain reaction reverse sequence-specific oligonucleotide (PCR-rSSO), which has already been applied to cancer tissue samples in the clinical setting. Concordance rates between plasma DNA and cancer tissues were 68% with MBP-QP and 66% with PCR-rSSO, indicating that these systems are equivalent in terms of detecting KRAS mutations with plasma DNA. KRAS mutations in plasma DNA were frequently observed in systemic metastatic cancer patients, and in three patients KRAS mutations appeared after chemotherapy containing anti-EGFR antibody. A prospective study is needed for clarifying whether KRAS mutations detected in plasma DNA are predictive markers of treatment efficacy with anti-EGFR antibody. More... »

PAGES

737-744

Identifiers

URI

http://scigraph.springernature.com/pub.10.1007/s12253-016-0175-1

DOI

http://dx.doi.org/10.1007/s12253-016-0175-1

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1032369772

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/28058585


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