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

Journal of Translational Medicine

Research

Maria Teresa Ionta¹  Mario Scartozzi¹  Valentina Doneddu²  Mario Budroni²  Francesco Tanda²  Antonio Cossu²  Panagiotis Paliogiannis²  Maria Colombino³  Antonella Manca³  Grazia Palomba³  Milena Casula³  Giuseppe Palmieri³  Antonio Pazzola⁴  Giovanni Sanna⁴  Carlo Putzu⁴  Efisio Defraia⁵  Annamaria Lanzillo⁵  Giovanni Baldino⁶  Luciano Virdis⁷  Michela Barca⁸  Giulia Gramignano⁸  Salvatore Ortu⁹  Tito Sedda^1,10  Giuseppina Sarobba^1,11  Francesca Capelli^1,11 

[1] Department of Medical Oncology, University of Cagliari, Cagliari, Italy;Department of Surgical, Microsurgical and Medical Sciences, University of Sassari, Viale San Pietro 43, 07100, Sassari, PC, Italy;Institute of Biomolecular Chemistry, CNR, Sassari, Italy;Medical Oncology Unit, University—Hospital of Sassari (AOU), Sassari, Italy;Oncology Unit, Businco Hospital, Cagliari, Italy;Oncology Unit, Civil Hospital, Alghero, Italy;Oncology Unit, Local Health Agency, Carbonia-Iglesias, Italy;Oncology Unit, Local Health Agency, Lanusei, Italy;Oncology Unit, Local Health Agency, Olbia, Italy;Oncology Unit, Local Health Agency, Oristano, Italy;Oncology Unit, Zonchello Hospital, Nuoro, Italy;

关键词: Colorectal cancer;    KRAS;    NRAS;    BRAF;    PIC3CA;   

DOI  :  10.1186/s12967-016-1053-z

 received in 2016-08-06, accepted in 2016-10-05,  发布年份 2016

来源: Springer

【 摘 要 】

BackgroundActivation 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.MethodsA 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.ResultsOverall, 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).ConclusionsOur study defines both prevalence and prognostic role of main activated oncogenes in a population-based large collection of CRC patients.

【 授权许可】

CC BY   
© The Author(s) 2016