İnvasiv Duktal Meme Karsinoması ile İlişkili Yanlış Anlamlı Mutasyonların Olası Yapısal ve Fonksiyonel Etkilerinin In Silico Tahmini ve Değerlendirilmesi

Abstract

Invasive Ductal Breast Carcinoma is an important problem in our country as it is in all over the world. For in situ breast cancer patients, the five-year survival rate is 52%, while for metastatic breast cancer patients this rate falls to 16%. Prevention and treatment of metastasis is the main focus of cancer research because of the high mortality rate and lack of an effective treatment. In this study, missense mutations, which were detected in İnvasive Ductal Breast Carcinoma and non-invasive breast carcinoma in situ Ductal Carcinoma, were obtained from the COSMIC database. Among these mutations, only those belonging to Invasive Ductal Breast Carcinoma were selected. In silico investigation of the effect of these mutations and finding mutations that have might have a deleterious effect on protein structure/function were aimed. The pathogenicity predictions of missense mutations were performed by using PredictSNP v1 and 69 genes with deleterious mutations were obtained. The pathways of the obtained genes were determined and ‘adherens junction’, which was thought to be one of the causes of Invasive Ductal Carcinoma invasion and metastasis, was selected. The mutations that were detected in genes (RHOA, Ep300, TCF7L2, CTNNB1, CREBBP, and EGFR), which belong to this pathway, were shown on three dimensional protein structures and the effect on protein structure/function was investigated. When literature search for mutations was made, it was observed that these mutations were also found in different cancers and it was shown that these mutations might also be important for invasive ductal breast carcinoma. For these reasons, our findings may provide meaningful results for the invasion and metastasis of Invasive Ductal Breast Carcinoma.