Salmaninejad Arash, Ghadami Shirin, Dizaji Majid Zaki, Golchehre Zahra, Estiar Mehrdad Asghari, Zamani Mohammad Reza, Ebrahimzadeh-Vesal Reza, Nowroozi Mohammad Reza, Shakoori Abbas
Clin Lab. 2015;61(7):749-59. doi: 10.7754/clin.lab.2014.141210.
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.
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.
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.
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.
前列腺癌是最常见的癌症之一，由特定基因的突变和/或其他基因改变引发。关于文献中先前的研究，主要突变发生在特定类型癌症的KRAS、BRAF和EGFR基因中。在本研究中，我们试图确定前列腺腺癌患者肿瘤组织标本中EGFR外显子18 - 21、KRAS密码子12、13和61以及BRAF密码子600突变的发生率和重要作用。此外，在本研究中，还尝试从生物信息学方面研究这些基因的分子特征。
从伊朗癌症研究所获取了总共35份富含肿瘤细胞的前列腺腺癌新鲜组织样本。通过直接桑格测序法确定KRAS密码子12、13和61、BRAF密码子600以及EGFR外显子18 - 21处是否存在突变。为了评估这些基因的分子特征、结构和翻译后修饰，使用SWISS - MODEL（http://swissmodel.expasy.org）和NetPhos 2.0（http://www.cbs.dtu.dk/services/NetPhos/）服务器进行了生物信息学调查。此外，使用生物信息学软件绘制了突变的系统发育树。
在35例前列腺腺癌中，有2例发现KRAS密码子12和13发生突变。2例在密码子12（G12V）和密码子13（G13D）的外显子2上携带纯合突变。此外，在任何样本中均未检测到BRAF密码子600和EGFR外显子18 - 21的突变。
基于前列腺腺癌患者群体，我们的研究表明KRAS密码子12和13的突变在前列腺癌中最为常见。注意到这些结果以及该基因的分子途径，该基因在前列腺癌发病机制中可能具有更明显的作用。然而，根据我们的发现，与先前的研究一样，BRAF和EGFR基因突变在前列腺腺癌中的作用小于KRAS基因，因此，我们认为KRAS基因的这些常见突变可作为前列腺腺癌早期诊断的早期确定标志物。未来，由于前列腺癌发展过程中病因参数的复杂性，迫切需要针对每个受影响个体进行病例特异性肿瘤分子鉴定和治疗。
