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Sökning: onr:"swepub:oai:DiVA.org:uu-428064" > Detection of KRAS m...

Detection of KRAS mutations in liquid biopsies from metastatic colorectal cancer patients using droplet digital PCR, Idylla, and next generation sequencing

Holm, Matilda (författare)
Univ Helsinki, Fac Med, Med, Dept Pathol, Helsinki, Finland.;Helsinki Univ Hosp, HUS Diagnost Ctr, HUSLAB, Helsinki, Finland.;Univ Helsinki, Fac Med, Res Programs Unit, Appl Tumor Genom Res Program, Helsinki, Finland.;Univ Helsinki, Fac Med, Dept Surg, Med, Helsinki, Finland.;Helsinki Univ Hosp, Helsinki, Finland.;Univ Helsinki, Fac Med, Res Programs Unit, Translat Canc Med Res Program, Helsinki, Finland.
Andersson, Emma (författare)
Helsinki Univ Hosp, HUS Diagnost Ctr, HUSLAB, Dept Genet, Helsinki, Finland.;Univ Helsinki, Helsinki, Finland.
Österlund, Emerik (författare)
Uppsala universitet,Experimentell och klinisk onkologi,Univ Helsinki, Fac Med, Dept Surg, Med, Helsinki, Finland.;Helsinki Univ Hosp, Helsinki, Finland.
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Ovissi, Ali (författare)
Univ Helsinki, Helsinki, Finland.;Helsinki Univ Hosp, HUS Diagnost Ctr, Dept Radiol, Helsinki, Finland.
Soveri, Leena-Maija (författare)
Helsinki Univ Hosp, Clin, Dept Oncol, Helsinki, Finland.;Hyvinkaa Hosp & Hyvinkaa Homecare, Hyvinkaa, Finland.
Anttonen, Anna-Kaisa (författare)
Helsinki Univ Hosp, HUS Diagnost Ctr, HUSLAB, Dept Genet, Helsinki, Finland.;Univ Helsinki, Helsinki, Finland.
Kytölä, Soili (författare)
Helsinki Univ Hosp, HUS Diagnost Ctr, HUSLAB, Dept Genet, Helsinki, Finland.;Univ Helsinki, Helsinki, Finland.
Aittomäki, Kristiina (författare)
Helsinki Univ Hosp, HUS Diagnost Ctr, HUSLAB, Dept Genet, Helsinki, Finland.;Univ Helsinki, Helsinki, Finland.
Osterlund, Pia (författare)
Univ Helsinki, Helsinki, Finland.;Helsinki Univ Hosp, Clin, Dept Oncol, Helsinki, Finland.;Tampere Univ Hosp, Dept Oncol, Tampere, Finland.;Tampere Univ, Fac Med & Life Sci, Tampere, Finland.
Ristimäki, Ari (författare)
Univ Helsinki, Fac Med, Med, Dept Pathol, Helsinki, Finland.;Helsinki Univ Hosp, HUS Diagnost Ctr, HUSLAB, Helsinki, Finland.;Univ Helsinki, Fac Med, Res Programs Unit, Appl Tumor Genom Res Program, Helsinki, Finland.
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Univ Helsinki, Fac Med, Med, Dept Pathol, Helsinki, Finland;Helsinki Univ Hosp, HUS Diagnost Ctr, HUSLAB, Helsinki, Finland.;Univ Helsinki, Fac Med, Res Programs Unit, Appl Tumor Genom Res Program, Helsinki, Finland.;Univ Helsinki, Fac Med, Dept Surg, Med, Helsinki, Finland.;Helsinki Univ Hosp, Helsinki, Finland.;Univ Helsinki, Fac Med, Res Programs Unit, Translat Canc Med Res Program, Helsinki, Finland. Helsinki Univ Hosp, HUS Diagnost Ctr, HUSLAB, Dept Genet, Helsinki, Finland.;Univ Helsinki, Helsinki, Finland. (creator_code:org_t)
2020-11-25
2020
Engelska.
Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 15:11
Relaterad länk:
https://doi.org/10.1...
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https://uu.diva-port... (primary) (Raw object)
https://journals.plo...
https://urn.kb.se/re...
https://doi.org/10.1...
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  • Tidskriftsartikel (refereegranskat)
Abstract Ämnesord
Stäng  
  • Circulating tumor DNA (ctDNA) is released from cancer cells and oncogenic mutations in ctDNA can be measured from plasma samples. Droplet digital PCR (ddPCR) is a sensitive and specific method for the detection of mutations in ctDNA. We analyzed serial plasma samples (n = 80) from ten metastatic colorectal cancer (mCRC) patients with a known KRAS mutation in their primary tumor. The patients were undergoing oncological treatment with bevacizumab in combination with alternating capecitabine and oxaliplatin or irinotecan. Baseline ddPCR KRAS mutation allele frequency (MAF) values ranged from 0% to 63%. The first radiologic response evaluation criteria in solid tumors (RECIST) evaluation was performed 45-63 days after the initiation of treatment, and by this time three patients had an undetectable level of KRAS mutation, one had a MAF value of 0.5%, and one had a MAF value of 3% that had been reduced by 95% from the baseline value. In three of these patients the RECIST assessment was stable disease and in two partial response. In seven patients, ddPCR MAF values increased before radiological disease progression or death, while one patient remained disease-free with an undetectable KRAS mutation level. Next, we analyzed all available plasma samples with the Idylla ctKRAS system (n = 60), and found that the overall degree of agreement between ddPCR and Idylla was almost perfect (kappa value = 0.860). We used next-generation sequencing (NGS) to detect treatment-induced mutations in the last serial plasma sample of each patient, but were unable to find any new mutations when compared to the primary tumor. This study shows that ddPCR and Idylla are equally efficient for the detection of KRAS mutations in the liquid biopsies from mCRC patients and that ctDNA may indicate the disappearance of treatment responsive KRAS positive mCRC clones and serve as an early sign of disease progression.

Ämnesord

MEDICIN OCH HÄLSOVETENSKAP  -- Klinisk medicin -- Cancer och onkologi (hsv//swe)
MEDICAL AND HEALTH SCIENCES  -- Clinical Medicine -- Cancer and Oncology (hsv//eng)

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