학술논문
Prognostic impact of KRAS, NRAS, BRAF, and PIK3CA mutations in primary colorectal carcinomas: a population-based study.
Document Type
Article
Author
Palomba, Grazia; Doneddu, Valentina; Cossu, Antonio; Paliogiannis, Panagiotis; Manca, Antonella; Casula, Milena; Colombino, Maria; Lanzillo, Annamaria; Defraia, Efisio; Pazzola, Antonio; Sanna, Giovanni; Putzu, Carlo; Ortu, Salvatore; Scartozzi, Mario; Ionta, Maria Teresa; Baldino, Giovanni; Sarobba, Giuseppina; Capelli, Francesca; Sedda, Tito; Virdis, Luciano
Source
Subject
*COLON cancer prognosis
*GENETIC mutation
*BRAF genes
*MEDICAL screening
*EPIDERMAL growth factor receptors
*POPULATION-based case control
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Language
ISSN
1479-5876
Abstract
Background: Activation of oncogenes downstream the EGFR gene contributes to colorectal tumorigenesis and determines the sensitivity to anti-EGFR treatments. The aim of this study was to evaluate the prognostic value of KRAS, BRAF, NRAS and PIK3CA mutations in a large collection of CRC patients from genetically-homogeneous Sardinian population. Methods: A total of 1284 Sardinian patients with histologically-proven diagnosis of colorectal carcinoma (CRC) and presenting with metastatic disease were included into the study. Genomic DNA was isolated from formalin-fixed, paraffin-embedded primary tumour tissue samples of CRC patients and screened for mutations in RAS and BRAF genes, using pyrosequencing assays, and in PIK3CA gene, using automated DNA sequencing assays. Results: Overall, mutation rates were 35.6% for KRAS, 4.1% for NRAS, and 2.1% for BRAF. Among available DNA samples, 114/796 (14.3%) primary CRCs were found to carry a mutation in the PIK3CA gene. In this subset of patients analysed in all four genes, a pathogenetic mutation of at least one gene was discovered in about half (378/796; 47.5%) of CRC cases. A mutated BRAF gene was found to steadily act as a negative prognostic factor for either time to progression as metastatic disease (from detection of primary CRC to diagnosis of first distant metastasis; p = 0.009) or partial survival (from diagnosis of advanced disease to the time of death or last control; p = 0.006) or overall survival (p < 0.001). No significant impact on prognosis was observed for mutated KRAS, NRAS, and PIK3CA genes or combined RAS mutations (all RAS). Conclusions: Our study defines both prevalence and prognostic role of main activated oncogenes in a populationbased large collection of CRC patients. [ABSTRACT FROM AUTHOR]