We found a match
Your institution may have access to this item. Find your institution then sign in to continue.
- Title
Mutations in the RAS-MAPK, PI(3)K (phosphatidylinositol-3-OH kinase) signaling network correlate with poor survival in a population-based series of colon cancers.
- Authors
Barault, Ludovic; Veyrie, Nicolas; Jooste, Valerie; Lecorre, Delphine; Chapusot, Caroline; Ferraz, Jean-Marc; Lièvre, Astrid; Cortet, Marion; Bouvier, Anne-Marie; Rat, Patrick; Roignot, Patrick; Faivre, Jean; Laurent-Puig, Pierre; Piard, Francoise
- Abstract
The RAS-MAPK, PI (3)K signaling pathways form a network that play a central role in tumorigenesis. The BRAF, KRAS and PI3KCA genes code 3 partners of this network and have been found to be activated by mutation in colorectal cancer; these mutations lead to unrestricted cell growth. We evaluated the clinicopathological features and the prognosis of patients with activated-network colon cancers in a population-based study. A total of 586 colon adenocarcinomas were evaluated using sequencing for mutations of KRAS and PI3KCA, and allelic discrimination for mutation of BRAF. Clinicopathological characteristics were correlated to the risk of bearing a mutation of the network using logistic regression. Three-year survival rates were compared with the Log rank test. A multivariate survival analysis using the Cox model was performed. After adjustment for age and microsatellite instability, activation of the network by mutation of at least 1 of the 3 genes was significantly associated with female sex ( p = 0.02) and proximal location ( p < 0.001). Lower levels of 3-year survival were associated with activation of the network by mutation of at least 1 of the 3 genes (59.4 and 69.4%, respectively; p = 0.009). These results remained significant in a multivariate analysis adjusted for sex, age, location, stage and microsatellite instability (HR = 1.48; CI CI
- Publication
International Journal of Cancer, 2008, Vol 122, Issue 10, p2255
- ISSN
0020-7136
- Publication type
Article
- DOI
10.1002/ijc.23388