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Abstract
Prostate cancer is one of the most common cancers which develops by mutations or/and other genetic alterations in specific genes. According to the recent studies there are predominant mutations occur in KRAS gene in different types of cancers. Missense mutations in codon 12 and codon 13 of KRAS proto-oncogene are main point mutations that happen in about 20% of diverse malignancies in human. The aim of this study is to find out the prevalence of two known main point mutations of KRAS gene (p.G12V/c.35G>T and p.G13D/c.38G>A) in addition to bioinformatics survey of its in Iranian patients with prostatic adenocarcinoma. A total of 35 prostatic adenocarcinoma fresh tissue samples that enriched in neoplastic cells, were obtained from the Cancer Institute of Iran. The presences of mutations at codons 12 and 13 of KRAS were investigated by direct Sanger sequencing. To investigate of the role of the mentioned mutations on structure and protein function, bioinformatics assessments were performed by using SWISS-MODEL server and the PSIPRED Protein Sequence Analysis software. KRAS mutations were detected in 2 of 35 patients (5.7%). Two cases carried the homozygote mutations on exon 2 in codon 12 (G12V) and codon 13 (G13D), respectively. Several prediction programs such as SIFT, Mutation Taster and polyphen-2 classified them as pathogenic. However, the bioinformatics survey shows that amino acid changes on codons 12/13 do not cause any probable disorder on protein structure, but effect on protein function. The result indicated that the protein function is modified. Based on the group of patients with prostate adenocarcinoma our study indicates that p.G12V/c.35G>T and p.G13D/c.38G>A mutations in codons 12 and 13 KRAS are most frequently occur in prostate carcinomas. The bioinformatics results from this study demonstrate that KRAS may have effects on pathogenesis of prostate cancer.
Highlights
The occurrence of prostate cancer (PC) is increasing worldwide, with strong dissimilarity among different regions
Out of 200 samples, 35 samples were prostatic adenocarcinoma fresh tissue samples that enriched in selected neoplastic cells
Structural point mutations in RAS proto-oncogene are common in human cancers including prostate cancer [17,19,21,22], and the mutation frequency varies, depending upon tumor types and stages [26,27]
Summary
The occurrence of prostate cancer (PC) is increasing worldwide, with strong dissimilarity among different regions It is one of the most common and leading causes of cancers deaths in many developed countries [1]. It is less common in developing countries, somewhat due to lack of nationwide screening program and not high quality cancer registration system [2,3], its incidence and mortality has been on the rise [4]. It is a major cause of morbidity and mortality in Iran [5,6]. The “gold standard” treatment for metastatic prostate cancer is androgen deprivation therapy (ADT) [7]
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