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BMC Cancer
Published in: BMC Cancer 1/2015

Open Access 01-12-2015 | Research article

Microsatellite instability and mutations in BRAF and KRAS are significant predictors of disseminated disease in colon cancer

Authors: Helgi Birgisson, Karolina Edlund, Ulrik Wallin, Lars Påhlman, Hanna Göransson Kultima, Markus Mayrhofer, Patrick Micke, Anders Isaksson, Johan Botling, Bengt Glimelius, Magnus Sundström

Published in: BMC Cancer | Issue 1/2015

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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.
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Metadata
Title
Microsatellite instability and mutations in BRAF and KRAS are significant predictors of disseminated disease in colon cancer
Authors
Helgi Birgisson
Karolina Edlund
Ulrik Wallin
Lars Påhlman
Hanna Göransson Kultima
Markus Mayrhofer
Patrick Micke
Anders Isaksson
Johan Botling
Bengt Glimelius
Magnus Sundström
Publication date
01-12-2015
Publisher
BioMed Central
Published in
BMC Cancer / Issue 1/2015
Electronic ISSN: 1471-2407
DOI
https://doi.org/10.1186/s12885-015-1144-x

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