title: Microsatellite instability and mutations in BRAF and KRAS are significant predictors of disseminated disease in colon cancer.
abstract: BACKGROUND
  Molecular alterations are well studied in colon cancer, however there is still need for an improved understanding of their prognostic impact. This study aims to characterize colon cancer with regard to KRAS, BRAF, and PIK3CA mutations, microsatellite instability (MSI), and average DNA copy number, in connection with tumour dissemination and recurrence in patients with colon cancer.
  
  
  METHODS
  Disease stage II-IV colon cancer patients (n = 121) were selected. KRAS, BRAF, and PIK3CA mutation status was assessed by pyrosequencing and MSI was determined by analysis of mononucleotide repeat markers. Genome-wide average DNA copy number and allelic imbalance was evaluated by SNP array analysis.
  
  
  RESULTS
  Patients with mutated KRAS were more likely to experience disease dissemination (OR 2.75; 95% CI 1.28-6.04), whereas the opposite was observed for patients with BRAF mutation (OR 0.34; 95% 0.14-0.81) or MSI (OR 0.24; 95% 0.09-0.64). Also in the subset of patients with stage II-III disease, both MSI (OR 0.29; 95% 0.10-0.86) and BRAF mutation (OR 0.32; 95% 0.16-0.91) were related to lower risk of distant recurrence. However, average DNA copy number and PIK3CA mutations were not associated with disease dissemination.
  
  
  CONCLUSIONS
  The present study revealed that tumour dissemination is less likely to occur in colon cancer patients with MSI and BRAF mutation, whereas the presence of a KRAS mutation increases the likelihood of disseminated disease.
authors.affiliation: Department of Surgical Sciences, Colorectal Surgery, Uppsala University, 75185, Uppsala, Sweden. helgi.birgisson@surgsci.uu.se.
authors.forename: Helgi
authors.initials: H
authors.lastname: Birgisson
authors.affiliation: Department of Immunology, Genetics and Pathology, Uppsala University, 75185, Uppsala, Sweden. karolina.edlund@ifado.de.
authors.forename: Karolina
authors.initials: K
authors.lastname: Edlund
authors.affiliation: Department of Surgical Sciences, Colorectal Surgery, Uppsala University, 75185, Uppsala, Sweden. ulrik-wallin@uiowa.edu.
authors.forename: Ulrik
authors.initials: U
authors.lastname: Wallin
authors.affiliation: Department of Surgical Sciences, Colorectal Surgery, Uppsala University, 75185, Uppsala, Sweden. lars.pahlman@surgsci.uu.se.
authors.forename: Lars
authors.initials: L
authors.lastname: Påhlman
authors.affiliation: Science for Life Laboratory, Department of Medical Sciences, Uppsala University, 75185, Uppsala, Sweden. Hanna.Goransson.Kultima@medsci.uu.se.
authors.forename: Hanna Göransson
authors.initials: HG
authors.lastname: Kultima
authors.affiliation: Science for Life Laboratory, Department of Medical Sciences, Uppsala University, 75185, Uppsala, Sweden. markus.mayrhofer@medsci.uu.se.
authors.forename: Markus
authors.initials: M
authors.lastname: Mayrhofer
authors.affiliation: Department of Immunology, Genetics and Pathology, Uppsala University, 75185, Uppsala, Sweden. patrick.micke@igp.uu.se.
authors.forename: Patrick
authors.initials: P
authors.lastname: Micke
authors.affiliation: Science for Life Laboratory, Department of Medical Sciences, Uppsala University, 75185, Uppsala, Sweden. Anders.Isaksson@medsci.uu.se.
authors.forename: Anders
authors.initials: A
authors.lastname: Isaksson
authors.affiliation: Department of Immunology, Genetics and Pathology, Uppsala University, 75185, Uppsala, Sweden. johan.botling@akademiska.se.
authors.forename: Johan
authors.initials: J
authors.lastname: Botling
authors.affiliation: Department of Radiology, Oncology and Radiation Science, Uppsala University, 75185, Uppsala, Sweden. bengt.glimelius@onkologi.uu.se.
authors.forename: Bengt
authors.initials: B
authors.lastname: Glimelius
authors.affiliation: Department of Immunology, Genetics and Pathology, Uppsala University, 75185, Uppsala, Sweden. magnus.sundstrom@igp.uu.se.
authors.forename: Magnus
authors.initials: M
authors.lastname: Sundström
mesh_terms: D000368:Aged; D003110:Colonic Neoplasms / Q000175:diagnosis* / Q000235:genetics*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D053842:Microsatellite Instability; D009154:Mutation / Q000235:genetics*; D011237:Predictive Value of Tests; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics*; D016283:Proto-Oncogene Proteins p21(ras); 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