title: Molecular Characterization of KRAS, BRAF, and EGFR Genes in Cases with Prostatic Adenocarcinoma; Reporting Bioinformatics Description and Recurrent Mutations.
abstract: BACKGROUND
  Prostate cancer is one of the most common cancers which develops by mutations and/or other genetic alterations in specific genes. Regarding the previous studies in literature predominant mutations take place in KRAS, BRAF, and EGFR genes in special types of cancers. In this research, we attempt to identify the prevalence and significant role of the possible mutations in EGFR exons 18-21, KRAS codon 12, 13, and 61, and BRAF codon 600 mutations in tumoral tissue specimens from patients with prostatic adenocarcinoma. Furthermore, in this research, it has been attempted to investigate the molecular characteristics of these genes in terms of bioinformatic aspects.
  
  
  METHODS
  A total of 35 prostatic adenocarcinoma fresh tissue samples, enriched in neoplastic cells, were obtained from the Cancer Institute of Iran. The presence of mutations at codons 12, 13 and 61 of KRAS, codon 600 of BRAF and EGFR exons 18-21 were determined by direct Sanger sequencing. To evaluate the molecular features, structure, and post-translation modification of those genes, a bioinformatics survey was performed using the SWISS-MODEL (http://swissmodel.expasy.org) and NetPhos 2.0 (http://www.cbs.dtu.dk/services/NetPhos/) Server. Also, using bioinformatics software, the phylogeny tree of the mutations was drawn.
  
  
  RESULTS
  Mutations of codons 12 and 13 of KRAS were found in 2 of the 35 prostatic adenocarcinomas. Two cases carried homozygous mutations on exon 2 in codon 12 (G12V) and codon 13 (G13D). Also, no mutation was detected at BRAF codon 600 and EGFR exons 18-21 in any of the samples.
  
  
  CONCLUSIONS
  Based on the group of patients with prostate adenocarcinoma, our research shows that the mutations in codons 12 and 13 of KRAS are the most common in prostate carcinomas. Noting these results and the molecular pathway of this gene, there is a possible more perceptible role for this gene in the pathogenesis of prostatic carcinoma. However, according to our finding, as in previous studies, the role of BRAF and EGFR gene mutations in prostate adenocarcinoma are less than in the KRAS gene and, therefore, we assume that these common mutations of the KRAS gene can be used as an early determining marker for early diagnosis of prostate adenocarcinoma. In the future, due to the complexity of etiological parameters in prostate cancer development, the case specific tumor molecular identification and treatment for each affected subject are urgently needed.
authors: Arash
authors: A
authors: Salmaninejad
authors: Shirin
authors: S
authors: Ghadami
authors: Majid Zaki
authors: MZ
authors: Dizaji
authors: Zahra
authors: Z
authors: Golchehre
authors: Mehrdad Asghari
authors: MA
authors: Estiar
authors: Mohammad Reza
authors: MR
authors: Zamani
authors: Reza
authors: R
authors: Ebrahimzadeh-Vesal
authors: Mohammad Reza
authors: MR
authors: Nowroozi
authors: Abbas
authors: A
authors: Shakoori
mesh_terms: D000230:Adenocarcinoma / Q000175:diagnosis* / Q000473:pathology; D000368:Aged; D003062:Codon; D019295:Computational Biology; D004252:DNA Mutational Analysis; D066246:ErbB Receptors / Q000737:chemistry / Q000235:genetics*; D005091:Exons; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006801:Humans; D007492:Iran; D008297:Male; D008875:Middle Aged; D008958:Models, Molecular; D009154:Mutation; D010641:Phenotype; D010802:Phylogeny; D011237:Predictive Value of Tests; D011379:Prognosis; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000473:pathology; D020836:Protein Structure, Quaternary; D011518:Proto-Oncogene Proteins / Q000737:chemistry / Q000235:genetics*; D048493:Proto-Oncogene Proteins B-raf / Q000737:chemistry / Q000235:genetics*; D016283:Proto-Oncogene Proteins p21(ras); D013329:Structure-Activity Relationship; D018631:ras Proteins / Q000737:chemistry / Q000235:genetics*
chemical_list: D003062:Codon; C117307:KRAS protein, human; D011518:Proto-Oncogene Proteins; C512478:EGFR protein, human; D066246:ErbB Receptors; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins