Tumor Biology

, Volume 37, Issue 5, pp 6823–6830 | Cite as

G12V and G12A KRAS mutations are associated with poor outcome in patients with metastatic colorectal cancer treated with bevacizumab

  • Ondrej Fiala
  • Tomas Buchler
  • Beatrice Mohelnikova-Duchonova
  • Bohuslav Melichar
  • Vit Martin Matejka
  • Lubos Holubec
  • Jana Kulhankova
  • Zbynek Bortlicek
  • Marie Bartouskova
  • Vaclav Liska
  • Ondrej Topolcan
  • Monika Sedivcova
  • Jindrich Finek
Original Article


The v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog (KRAS) mutations are found in 35–45 % of colorectal cancer (CRC) cases. Although the association between the RAS signaling and angiogenesis is well known, the negative predictive value of KRAS mutation has not been established in patients treated with bevacizumab. The aim of this study was to evaluate the association between specific KRAS mutation types and outcome of patients with metastatic CRC treated with bevacizumab. The study included 404 patients with metastatic CRC (mCRC) treated with bevacizumab. Clinical data obtained from the clinical registry CORECT were retrospectively analyzed. The shortest survival was observed in patients with tumors harboring G12V or G12A KRAS mutation (G12V/A). The median progression-free survival (PFS) and overall survival (OS) for patients with tumors harboring G12V/A KRAS mutation was 6.6 and 16.8 compared to 11.6 and 26.3 months for patients with tumors harboring other KRAS mutation type (p < 0.001 and p < 0.001), while the survival of patients harboring other KRAS mutation types was comparable to those with tumors harboring wild-type KRAS gene. In the Cox multivariable analysis, KRAS G12V/A mutation type remains a significant factor predicting both PFS (HR = 2.18, p < 0.001) and OS (HR = 2.58, p < 0.001). In conclusion, the results of the present study indicate that there is a significant difference in biological behavior between tumors harboring G12V/A and other KRAS mutations. Moreover, comparison of the survival of patients with tumors harboring G12V/A KRAS mutations with those harboring wild-type KRAS gene revealed that G12V/A KRAS mutations are prognostic biomarker for inferior PFS and OS in patients with mCRC treated with bevacizumab in univariate as well as multivariable analyses.


Colorectal cancer Bevacizumab Chemotherapy KRAS Mutation 



The authors would like to thank all patients voluntarily taking part in the observational, population-based registry CORECT. This study was supported by the National Sustainability Program I (NPU I) Nr. LO1503 provided by the Ministry of Education Youth and Sports of the Czech Republic.

Compliance with ethical standards

Conflicts of interest

JF has received honoraria from Astra Zeneca, Roche, and Novartis for consultations and lectures unrelated to this project. BM has received honoraria from Astra Zeneca, Roche, Merck, Amgen, and Novartis for consultations and lectures unrelated to this project. TB has received honoraria from Roche for consultations and lectures unrelated to this project. OF, VMM, LH, JK, ZB, MB, VL, OT, and MS declare that they have no actual or potential conflict of interest including any financial, personal, or other relationships with other people or organizations that could inappropriately influence this work.

Supplementary material

13277_2015_4523_MOESM1_ESM.docx (22 kb)
ESM 1 (DOCX 22 kb)


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Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2015

Authors and Affiliations

  • Ondrej Fiala
    • 1
    • 2
  • Tomas Buchler
    • 3
  • Beatrice Mohelnikova-Duchonova
    • 4
  • Bohuslav Melichar
    • 4
  • Vit Martin Matejka
    • 1
  • Lubos Holubec
    • 1
  • Jana Kulhankova
    • 1
  • Zbynek Bortlicek
    • 5
  • Marie Bartouskova
    • 4
  • Vaclav Liska
    • 2
    • 6
  • Ondrej Topolcan
    • 7
  • Monika Sedivcova
    • 8
  • Jindrich Finek
    • 1
  1. 1.Department of Oncology and Radiotherapy, Medical School and Teaching Hospital PilsenCharles University in PraguePilsenCzech Republic
  2. 2.Biomedical Center, Faculty of Medicine in PilsenCharles University in PraguePlzeňCzech Republic
  3. 3.Department of Oncology and First Faculty of MedicineCharles University and Thomayer HospitalPragueCzech Republic
  4. 4.Department of OncologyPalacký University Medical School and Teaching HospitalOlomoucCzech Republic
  5. 5.Institute of Biostatistics and Analyses, Faculty of MedicineMasaryk UniversityBrnoCzech Republic
  6. 6.Department of Surgery, Medical School and Teaching Hospital PilsenCharles University in PraguePilsenCzech Republic
  7. 7.Department of Nuclear Medicine, Medical School and Teaching Hospital PilsenCharles University in PraguePilsenCzech Republic
  8. 8.Bioptic Laboratory, Ltd., Molecular Pathology LaboratoryPlzeňCzech Republic

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