Prevalence of k-ras Mutation in Ovarian Cancer Patients in Tabriz

Bagherlou, Nazanin and Zahri, Saber and Farajnia, Safar and Dastranj Tabrizi, Ali (2015) Prevalence of k-ras Mutation in Ovarian Cancer Patients in Tabriz. Masters thesis, University of Mohaghegh Ardabili.

Text (بررسي شيوع موتاسيون ژن K-ras در بيماران مبتلا به سرطان تخمدان در شهر تبريز) Nazanin Bagherlou.pdf Download (730kB)

Abstract

Background: Ovarian carcinoma is the most lethal cancer. Its frequency has increased in the last decade.The K-ras gene encodes the K-Ras protein, an important component of the tyrosine kinase signaling Ras/MAPK pathway. The K-Ras protein functions as a binary switch, binds to GDP in its inactive state and GTP in the active. To inactivate itself, the K-Ras protein interacts with GTPase-activating proteins and, when bound to GDP, it is not able to transmit signals to the cell nucleus. Mutations in the K-ras gene abolish the GTPase function and, for this reason, lead to a constitutively activated protein that cannot turn itself off . For this reasons, K-ras mutations, most commonly affecting codons 12 has been described in different types from tumors. Anti EGFR antibodies are new and efficient theraputics for cancers with high level expression of EGFR, but it has shown that cancers with mutated K-ras are resistant to these class of therapeutics. Hence, determination of mutation in K-ras gene is important in predicting response to Anti-EGFR therapies. This study aimed to compare the prevalence of K-ras gene (codon 12 and codon 13) mutations in patients with ovarian cancer Method: Genomic DNA was extracted from 67 parrafin embedded tissues pertained to women with ovarian cancer. Samples were obtained from gynecology department of Alzahra hospital in Tabriz. Mutation in codon 12 and codon 13 of K-ras were analyzes with Nested polymerase chain reaction (Nested-PCR) technique and BSTN1 and VAN91 I as a restriction enzyme. A statistical analysis was performed by chi-square test using spss software. A P value < 0.05 was considered statistically significant. Results: In our study none of 67 patients had mutations in codon 13 whrereas 7 of them had mutation in codon 12 of K-ras gene.The frequencies observed, GG,GA and AA in codon 12 of K-ras gene were 89.55%,10.44% and 0% in patients. In this study when malignant samples were compared with respect to histology, the mutational rate in mucinous lesions was significantly higher than in lesions of other histotypes, P value was acquired 0.001 and the mutation rates are significant higher in grade 1 and 2 of carcinoma compared to grade 3 and 4 of tumors P value was acquired 0.04 and statistically significant correlation was found between codon 12 mutation and stage 1 in ovarian cancer but no correlation was found between codon13 and ovarian cancer. The results of this study show that mutation in codon 12 is significantly correlated with ovarian cancers. Keywords: Codon 12, K-ras, Ovarian cancer, RFLP,

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