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

Overview of attention for article published in Journal of Translational Medicine, October 2016
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Title
Prognostic impact of KRAS, NRAS, BRAF, and PIK3CA mutations in primary colorectal carcinomas: a population-based study
Published in
Journal of Translational Medicine, October 2016
DOI 10.1186/s12967-016-1053-z
Pubmed ID
Authors

Grazia Palomba, Valentina Doneddu, Antonio Cossu, Panagiotis Paliogiannis, Antonella Manca, Milena Casula, Maria Colombino, Annamaria Lanzillo, Efisio Defraia, Antonio Pazzola, Giovanni Sanna, Carlo Putzu, Salvatore Ortu, Mario Scartozzi, Maria Teresa Ionta, Giovanni Baldino, Giuseppina Sarobba, Francesca Capelli, Tito Sedda, Luciano Virdis, Michela Barca, Giulia Gramignano, Mario Budroni, Francesco Tanda, Giuseppe Palmieri

Abstract

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. 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. 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). Our study defines both prevalence and prognostic role of main activated oncogenes in a population-based large collection of CRC patients.

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Mendeley readers

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The data shown below were compiled from readership statistics for 73 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 73 100%

Demographic breakdown

Readers by professional status Count As %
Researcher 15 21%
Student > Master 11 15%
Student > Bachelor 9 12%
Student > Ph. D. Student 7 10%
Other 4 5%
Other 6 8%
Unknown 21 29%
Readers by discipline Count As %
Biochemistry, Genetics and Molecular Biology 19 26%
Medicine and Dentistry 19 26%
Agricultural and Biological Sciences 4 5%
Philosophy 1 1%
Immunology and Microbiology 1 1%
Other 3 4%
Unknown 26 36%
Attention Score in Context

Attention Score in Context

This research output has an Altmetric Attention Score of 1. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 13 October 2016.
All research outputs
#15,387,502
of 22,893,031 outputs
Outputs from Journal of Translational Medicine
#2,239
of 4,007 outputs
Outputs of similar age
#201,266
of 319,475 outputs
Outputs of similar age from Journal of Translational Medicine
#42
of 73 outputs
Altmetric has tracked 22,893,031 research outputs across all sources so far. This one is in the 22nd percentile – i.e., 22% of other outputs scored the same or lower than it.
So far Altmetric has tracked 4,007 research outputs from this source. They typically receive a lot more attention than average, with a mean Attention Score of 10.5. This one is in the 31st percentile – i.e., 31% of its peers scored the same or lower than it.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 319,475 tracked outputs that were published within six weeks on either side of this one in any source. This one is in the 28th percentile – i.e., 28% of its contemporaries scored the same or lower than it.
We're also able to compare this research output to 73 others from the same source and published within six weeks on either side of this one. This one is in the 10th percentile – i.e., 10% of its contemporaries scored the same or lower than it.