title: KRAS and BRAF mutations in Serbian patients with colorectal cancer.
abstract: OBJECTIVE
  Mutations of KRAS and BRAF genes represent molecular biomarkers of response to targeted therapy in patients with metastatic colorectal cancer (mCRC). Since these mutations have been shown to exert different biological effects and impacts on patients' outcome, there is a need to determine reliably the frequency and types of KRAS mutations for diagnostic and individual therapeutic purposes. Despite having a wild type (wt) KRAS, some patients fail to respond to treatment. BRAF V600E mutation is an additional molecular determinant of response to the same therapy. In this study we described the KRAS and the BRAF V600E mutation spectra and frequencies in a group of Serbian mCRC specimens.
  
  
  METHODS
  KRAS mutations were determined with DxS TheraScreen® K-RAS Mutation Kit and KRAS StripAssay(™), and for the BRAF V600E mutation we applied High Resolution Melting (HRM) analysis.
  
  
  RESULTS
  KRAS mutations were present in 34.7% of 190 analyzed samples. The 7 most frequent mutation types observed were: G12D 43.9%, G12V 21.2%, G12A 10.6%, G12C 7.6%, G12S 4.5%, G12R 1.5%, G13D 10.6%. Among the wt KRAS patients, 17.8% carried the BRAF V600E mutation.
  
  
  CONCLUSIONS
  We have shown that the spectrum and frequency distribution of the identified KRAS and BRAF mutations in Serbian study population are in good accordance with literature data. We believe that our results are significant concerning aspects related to tumor molecular biology as well as to patient selection in the diagnostic settings.
authors.affiliation: Institute for Oncology and Radiology of Serbia, Department of Experimental Oncology, Belgrade, Serbia. jankovicr@ncrc.ac.rs
authors.forename: K
authors.initials: K
authors.lastname: Jakovljevic
authors.forename: E
authors.initials: E
authors.lastname: Malisic
authors.forename: M
authors.initials: M
authors.lastname: Cavic
authors.forename: A
authors.initials: A
authors.lastname: Krivokuca
authors.forename: J
authors.initials: J
authors.lastname: Dobricic
authors.forename: R
authors.initials: R
authors.lastname: Jankovic
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015179:Colorectal Neoplasms / Q000235:genetics*; D006801:Humans; D007223:Infant; D008297:Male; D008875:Middle Aged; D009154:Mutation; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics*; D016283:Proto-Oncogene Proteins p21(ras); D055771:Serbia; D018631:ras Proteins / Q000235:genetics*
chemical_list: C117307:KRAS protein, human; D011518:Proto-Oncogene Proteins; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins