Prognostic impact of KRAS, NRAS, BRAF, and PIK3CA mutations in primary colorectal carcinomas: a population-based study

Autor: Giuseppina Sarobba, Giulia Gramignano, Antonella Manca, Milena Casula, Tito Sedda, Salvatore Ortu, Panagiotis Paliogiannis, Efisio Defraia, Giuseppe Palmieri, Francesca Capelli, Carlo Putzu, Maria Colombino, Luciano Virdis, Antonio Cossu, Mario Scartozzi, Francesco Tanda, Antonio Pazzola, Maria Teresa Ionta, Giovanni Sanna, Giovanni Baldino, Michela Barca, Annamaria Lanzillo, Grazia Palomba, Valentina Doneddu, Mario Budroni
Rok vydání: 2016
Předmět:
0301 basic medicine
Neuroblastoma RAS viral oncogene homolog
Oncology
Male
Mutation rate
Colorectal cancer
Kaplan-Meier Estimate
medicine.disease_cause
GTP Phosphohydrolases
0302 clinical medicine
Mutation Rate
Medicine(all)
Aged
80 and over
Mutation
education.field_of_study
medicine.diagnostic_test
Geography
General Medicine
Middle Aged
Prognosis
Mutation analysis
Italy
030220 oncology & carcinogenesis
Female
KRAS
Colorectal Neoplasms
Adult
Proto-Oncogene Proteins B-raf
medicine.medical_specialty
Class I Phosphatidylinositol 3-Kinases
Population
NRAS
General Biochemistry
Genetics and Molecular Biology
PIC3CA
BRAF
Proto-Oncogene Proteins p21(ras)
03 medical and health sciences
Internal medicine
medicine
Humans
Genetic Testing
education
neoplasms
Genetic Association Studies
Genetic testing
Aged
Biochemistry
Genetics and Molecular Biology(all)
Research
Membrane Proteins
PIK3CA
medicine.disease
digestive system diseases
030104 developmental biology
Cancer research
Zdroj: Journal of Translational Medicine
Journal of translational medicine (Online) 14 (2016): 1–11. doi:10.1186/s12967-016-1053-z
info:cnr-pdr/source/autori:Palomba G.; Doneddu V.; Cossu A.; Paliogiannis P.; Manca A.; Casula M.; Colombino M.; Lanzillo A.; Defraia E.; Pazzola A.; Sanna G.; Putzu C.; Ortu S.; Scartozzi M.; Ionta M.T.; Baldino G.; Sarobba G.; Capelli F.; Sedda T.; Virdis L.; Barca M.; Gramignano G.; Budroni M.; Tanda F.; Palmieri G./titolo:Prognostic impact of KRAS, NRAS, BRAF, and PIK3CA mutations in primary colorectal carcinomas: A population-based study/doi:10.1186%2Fs12967-016-1053-z/rivista:Journal of translational medicine (Online)/anno:2016/pagina_da:1/pagina_a:11/intervallo_pagine:1–11/volume:14
ISSN: 1479-5876
DOI: 10.1186/s12967-016-1053-z
Popis: 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
Databáze: OpenAIRE
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