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KAYA, HANDAN

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KAYA

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2009 - 200912010 - 20201
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Author: AKKİPRİK, MUSTAFA × Subject: Breast cancer ×

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    PIK3CA and TP53 MUTATIONS and SALL4, PTEN and PIK3R1 GENE EXPRESSION LEVELS in BREAST CANCER
    (WALTER DE GRUYTER GMBH, 2020) KAYA, HANDAN; Dirican, Ebubekir; Seven, Ipek Erbarut; Kaya, Handan; Ugurlu, M. Umit; Peker, Irem; Gulluoglu, Bahadir M.; Ozer, Ayse; Akkiprik, Mustafa
    Objective: A high frequency of PI3K signalling pathway abnormalities and TP53 mutations are critical in the development and progression of breast cancer (BCa). We aimed to detect PIK3CA and TP53 mutations via an expression analysis of PIK3R1, PTEN and SALL4 and correlate the expression of these genes with clinical parameters of BCa. Materials and methods: PIK3CA and TP53 mutations in BCa samples were analysed by High-Resolution Melting (HRM) analysis, followed by Sanger sequencing, and the expression levels of PIK3R1, PTEN and SALL4 were evaluated by RT-PCR methods. Results: The frequency of PIK3CA and TP53 mutations was 42% and 38% according to the HRM and Sanger sequencing. There was a significantly high frequency of these mutations in ER(+), N0 and HER2(-) tumour samples. PIK3R1 and PTEN expression levels were high in tumour samples, whereas SALL4 expression was low. In patients with TP53 mutations, PIK3R1 expression was low, and this finding was statistically significant. PIK3R1 and PTEN expression levels showed statistically significant, respectively in G3 grades, ER(+), (PR)(+), HER2(+) and ER(+). Conclusions: We suggest that these candidate genes could be potential prognostic biomarkers of BCa and that they should be considered in the evaluation of clinical parameters of BCa.
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    Analysis of p53 Gene Polymorphisms and Protein Over-expression in Patients with Breast Cancer
    (SPRINGER, 2009) KAYA, HANDAN; Akkiprik, Mustafa; Sonmez, Ozgur; Gulluoglu, Bahadir M.; Caglar, Hale B.; Kaya, Handan; Demirkalem, Pakize; Abacioglu, Ufuk; Sengoz, Meric; Sav, Aydin; Ozer, Ayse
    p53 polymorphic variants play an important role in the determination of tumor phenotype and characteristics in breast cancer. In this study, we examined three common polymorphisms in p53 gene and their haplotype combinations to assess their potential association with inherited predisposition to breast cancer development, in relations with the protein over-expression and patients' demographic data. A total of 99 patients with breast cancer and 107 age-matched healthy controls were included in the study. Genotypes were determined using PCR-RFLP and DNA sequencing techniques. Evaluation of p53 protein overexpression was also examined by immunohistochemistry. Among three polymorphisms, increased codon 72 Pro allele frequency (p=0.0067) and the presence of Pro allele were found to be significantly associated with breast cancer (p=0.013). A significant risk was also found in subjects with combinations of specific haplotypes and genotypes. Most of breast cancer women especially younger than 50 years carry at least one p53 polymorphism (p=0.001). There was no any association between these three p53 polymorphisms and the protein over-expression, separately or in interaction, with breast cancer. In conclusion, presence of proline allele at codon 72 alone, and its special combinations with other two polymorphisms appear to be a significant risk factor for breast cancer. Determination of well-known p53 polymorphisms might be a good predictor for breast cancer development especially in women younger than 50 years.