Prognostic impact of KRAS, NRAS, BRAF, and PIK3CA mutations in primary colorectal carcinomas: a population-based study.
J Transl Med
; 14(1): 292, 2016 10 13.
Article
en En
| MEDLINE
| ID: mdl-27737711
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 population-based large collection of CRC patients.Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Contexto en salud:
2_ODS3
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6_ODS3_enfermedades_notrasmisibles
Problema de salud:
2_muertes_prematuras_enfermedades_notrasmisibles
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6_colon_rectum_cancers
Asunto principal:
Neoplasias Colorrectales
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Proteínas Proto-Oncogénicas p21(ras)
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Proteínas Proto-Oncogénicas B-raf
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Fosfatidilinositol 3-Quinasa Clase I
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GTP Fosfohidrolasas
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Proteínas de la Membrana
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Mutación
Tipo de estudio:
Prognostic_studies
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Risk_factors_studies
Límite:
Adult
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Aged
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Aged80
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Female
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Humans
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Male
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Middle aged
País/Región como asunto:
Europa
Idioma:
En
Revista:
J Transl Med
Año:
2016
Tipo del documento:
Article
País de afiliación:
Italia