Elif Z Akisik

Publications (4)5.31 Total impact

• Chapter: H3K9me3/H4K20me3 Ratio in Circulating Nucleosomes as Potential Biomarker for Colorectal Cancer

  Ugur Deligezer, Elif Z. Akisik, Ebru E. Akisik, Müge Kovancilar, Dursun Bugra, Nilgün Erten, Stefan Holdenrieder, Nejat Dalay
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  ABSTRACT: Detection of cancer-related histone modifications of nucleosomes in the circulating blood may be useful in early cancer diagnosis. We have analyzed the trimethylation of histone H3 lysine 9 (H3K9me3) and histone H4 lysine 9 (H4K20me3), two modifications involved in heterochromatin formation, at pericentric heterochromatin of circulating nucleosomes in the blood plasma of healthy individuals, patients with either colorectal cancer or multiple myeloma. H3K9me3 was found to be decreased in colorectal cancer and increased in multiple myeloma while H4K20me3 levels were similar in all study groups. Therefore, we used the H3K9me3/H4K20me3 ratio for normalizing H3K9me3 concentrations; it significantly distinguished patients with colorectal cancer (median 0.8) from the healthy group (median 3) and multiple myeloma (median 4.7) (both p < 0.001). We conclude that if validated in a larger series of cases the ratio H3K9me3/H4K20me3 might be a potential diagnostic biomarker for colorectal cancer. KeywordsColorectal cancer-Circulating nucleosomes-Histone methylation-Plasma-Sat2 repeat
  12/2010: pages 97-103;
• Source

  Available from: Regina Santella

  Article: Investigation of the miR16-1 (C > T) + 7 Substitution in Seven Different Types of Cancer from Three Ethnic Groups.

  Hulya Yazici, Jennifer Zipprich, Tao Peng, Elif Z Akisik, Hulya Tigli, Mustafa Isin, Ebru E Akisik, Mary Beth Terry, Ruby T Senie, Lequn Li, Minhao Peng, Zhiming Liu, Nejat Dalay, Regina M Santella
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  ABSTRACT: Background. MicroRNAs are a type of small noncoding RNA molecules that have been shown to control gene expression in eukaryotes. Aberrant expression and alteration of miRNAs may be responsible for human diseases including cancer. An miR16-1 (C > T) + 7 gene mutation has been previously found in familial chronic lymphocytic leukemia patients, one of which reported a family history of breast cancer. miR16-1 regulates the expression of bcl-2, which is important in retinoblastoma, and is located in a genomic region that is frequently lost in nasopharyngeal and hepatocellular carcinomas (HCCs). Therefore, miR16-1 may be potentially important in the etiology of several solid tumors. To understand the power of the miR16-1 (C > T) + 7 mutation as a prognostic and diagnostic risk factor, we investigated the mutation in patients with seven different types of cancer including 188 with breast, 102 with ovarian, and 22 nasopharyngeal carcinomas, 96 HCC, 872 chronic myeloid leukemia (CML), 39 chronic lymphocytic leukemia (CLL), and 46 retinoblastoma cases from three different ethnic groups and of hereditary and sporadic etiology. Methods. 5'Nuclease TaqMan SNP genotyping assay was used to detect the miR16-1 gene C > T substitution. Results. The miR16-1 (C > T) + 7 substitution was not detected in any of the groups studied. Conclusions. Considering the large scale of our study, the representation of different ethnicities and levels of hereditary risk, we conclude that the miR-16-1 (C > T) + 7 mutation is not a good diagnostic or prognostic indicator of risk for the cancers tested.
  Journal of Oncology 01/2009; 2009:827532.
• Source

  Available from: yesimeralp.com

  Article: Effect of adjuvant chemotherapy on integrity of free serum DNA in patients with breast cancer.

  Ugur Deligezer, Yesim Eralp, Elif Z Akisik, Ebru E Akisik, Pinar Saip, Erkan Topuz, Nejat Dalay
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  ABSTRACT: It is not known how chemotherapy-induced cell death influences the size distribution of circulating free DNA (cf-DNA) in serum or plasma of cancer patients. In the present study, we investigated the integrity of cf-DNA during adjuvant systemic therapy in patients (n= 41) with invasive breast cancer. Sera taken at the beginning and the end of the adjuvant chemotherapy were comparatively analyzed for the integrity of cf-DNA. The assay was based on quantification of shorter and longer fragments representing apoptotic or non-apoptotic DNA from abundant genomic ALU repeats by quantitative real-time PCR. The ratio of longer to shorter fragments showed the integrity of free serum DNA. During chemotherapy, in half of the patients (51.2%), total DNA levels increased, but decreased in the other half. The distribution of the DNA integrity in the whole patient group after the systemic therapy (median 0.31) did not significantly differ from that at the beginning (median 0.29, P= 0.39). However, in the subgroups, the variation of the DNA integrity was related to the course of the total DNA level. In the subgroup with an increasing DNA level, the median DNA integrity was elevated from 0.27 to 0.39 (P= 0.005), whereas in the group with a decrease it declined from 0.34 to 0.28 (P= 0.044). Our results show that longer fragments released from non-apoptotic cells are the main contributors to increasing DNA levels during adjuvant systemic therapy. This information might be helpful in evaluating the response of patients to adjuvant systemic therapy.
  Annals of the New York Academy of Sciences 09/2008; 1137:175-9. · 3.15 Impact Factor
• Article: Size distribution of circulating cell-free DNA in sera of breast cancer patients in the course of adjuvant chemotherapy.

  Ugur Deligezer, Yesim Eralp, Ebru E Akisik, Elif Z Akisik, Pinar Saip, Erkan Topuz, Nejat Dalay
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  ABSTRACT: The integrity of circulating cell-free DNA (cf-DNA) in serum or plasma appears to be of diagnostic and prognostic value in cancer. Here, we investigated the dynamics of serum DNA levels and the size distribution of cf-DNA during adjuvant chemotherapy of patients with breast cancer (n=73). By evaluating sera taken at the beginning and the end of the adjuvant chemotherapy, variations of serum DNA levels and the size distribution were analyzed, based on quantification of shorter apoptotic and longer non-apoptotic fragments from abundant genomic ALU fragments amplified by quantitative real-time PCR. The mean DNA level did not change significantly during chemotherapy. However, individual cases revealed considerable variation in the amount of serum DNA. It increased in 43.8% of the patients, whereas it decreased in the remaining majority (56.2%). By calculating a "coefficient of variation" (both decrease and increase) in the level of total DNA and non-apoptotic DNA fragments, we compared the values at the beginning and the end of the therapy. For total DNA, the range was between 1.02- and 26-fold (mean 3.76-fold), whereas for non-apoptotic fragments it ranged from 1.01- to 73-fold (mean 6.9-fold) (p=0.033). In accordance with these findings, the integrity of serum DNA was higher in patients with increasing DNA levels and vice versa. Our findings suggest that non-apoptotic fragments contribute to a higher degree to the change of the DNA level during adjuvant chemotherapy.
  Clinical Chemistry and Laboratory Medicine 02/2008; 46(3):311-7. · 2.15 Impact Factor