Objective: The aim of this study was to determine the expression levels of CDH1, FHIT, and TTPAL genes and to determine the genotype and allele frequencies of the IL7Ralpha gene polymorphism ...rs6897932 in patients with breast cancer. Methods: The expression levels of genes and the distribution of the IL7Ralpha gene polymorphism rs6897932 were analyzed by real-time polymerase chain reaction. Results: No differences in genotype ratios or allele frequencies were observed between the 2 groups for the IL7Ralpha gene polymorphism rs6897932. The frequency of the IL7Ralpha rs6897932 T risk allele was found to be similar between breast cancer patients and controls. CDH1 messenger RNA (mRNA) levels decreased (0.714-fold and 0.834-fold, respectively), and TTPAL mRNA levels increased (2.675-fold P < .05 and 1.169-fold, respectively) in tumor tissues and peripheral blood samples. FHIT mRNA levels decreased (0.559-fold) in tumor tissue samples and increased (2.21-fold) in peripheral blood samples. Conclusion: Our results are compatible with those reported in the literature. It can be suggested that the upregulation observed in the TTPAL gene might be a marker for breast cancer. The downregulation of CDH1 and FHIT gene expression has been validated in our study. An increase in the copy numbers of FHIT mRNA in blood samples and a decrease in the tumor samples can also be considered an abnormal condition. P R Health Sci J 2023;42(4):283-290 Key words: CDH1, FHIT, TTPAL, IL7Ralpha, rs6897932, Breast cancer
Abstract
Epigenetic modifications, particularly DNA methylation in selected gene promoters is a pivotal role in the development of colorectal cancer. DNA methylation is considered as one of the most ...important epigenetic mechanisms and it is catalyzed by DNA methyltransferases (DNMTs). DNMT1 abundance has been frequently seen in colorectal cancers but the reasons are not well understood. We investigated to the effect of chemotherapeutics used in treatment of colorectal cancer on expression of DNMT1 and this effect is achieved over which signalling pathway. In this study, GSK3β; IWP2 for β-catenin) and chemotherapeutics (oxaliplatin, fluorouracil, irinotecan) were detected by WST1. DNMT1 expression level was determinated by real-time PCR; and protein levels of GSK3β, pGSK3β(Ser9), Akt1, pAkt1(Ser473), β-catenin, pβ-catenin(Ser675) and DNMT1 by western blot. Our results indicated taht Akt1 increased the protein level of DNMT1 expression with coordinate transcriptional change via β-catenin pathway. Fluorouracil and irinotecan decreased DNMT1 expression at both transcriptional and translational levels but not oxaliplatin. Oxaliplatin increased DNMT1 expression at mRNA and protein levels. This effect is achieved by specific phosphorylation of β-catenin protein. The results revealed that use of some chemotherapeutic, particularly oxaliplatin, with spesific inhibitors (such as β-catenin inhibitor) in combination led to a reduced DNMT1 expression. Our findings may offer a new approach for determining the molecular effects of β-catenin signal pathway on DNMT1. This may allow us to identify new molecular targets for the treatment of colorectal cancers. However, the results revealed that some chemotherapeutics may contribute the aberration of DNA methylation.
Citation Format: NURAY VAROL, SUNA ARIKAN TERZİ, ZAFER SOYLEMEZ, HANDAN YILDIZ, MUJGAN OZDEMİR, MUSTAFA SOLAK. Does chemotherapeutics contribute to DNMT1 expression level in colorectal cancer cells abstract. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 5386. doi:10.1158/1538-7445.AM2017-5386
Introduction: Bipolar disorder (BD) is a serious psychiatric disorder characterized by mood swings (depressive and manic phases) that can strongly affect the quality of life of patients and their ...families. The lifetime prevalence of BD in the general population is 1%. The pathogenesis of BD is unknown; however, comprehensive epidemiological studies have shown that both genetic and environmental factors play a role. Within the scope of the current project, we aim to determine the genetic change responsible for the emergence of the disease and to make a genotype-phenotype correlation. Methods: In this study, we evaluated single nucleotide gene variants in three families (n = 6 patients) with bipolar disorder using whole-exome sequencing. Results: Seven genes (TMTC1, DGKH, STARD9, ITIH1, MARCKS, CSMD1, and ADRA2B) were identified as possibly associated with BPD. In addition, two novel variants were presented in the TMTC1 (c.1214T>G) and STARD9 (c.8288C>G) genes. Conclusion: Prospective studies in larger patient groups are required to determine the role of these genes in the etiology of the disease and their potential in diagnosis and treatment. To the best of our knowledge, this is the first methodically comprehensive study conducted in our country and can contribute to the identification of genes that may be associated with BD and the etiopathogenesis of the disease.
This study aimed to determine IDH1 R132H codon and the mRNA levels of PDK1, SLC2A1, EGFR, PTEN, and CD276 genes in brain tumors.
This study included 15 brain tumor tissues pituitary adenoma (1), ...pilocytic astrocytoma (1), mixed meningioma (2), mesothelial meningioma (2), atypical meningioma (1), immature teratoma (1), glioblastoma (4), meningioma (2), and bladder cancer metastasis (1). The expression levels of genes in brain tumor tissues were analyzed using real-time PCR. Sanger sequencing was performed to identify the IDH1 gene R132H codon.
All cases were wild-type in terms of IDH1 R132H: nucleotide 395 G A; codon CGT CAT. The mRNA level of PDK1 was lower in grade I tumor tissues (0.675-fold) and increased in grades II-III-IV (7.135, 16.912, and 7.081-fold, respectively) (P 0.001). The mRNA level of SLC2A1 decreased in all grades I-II-III-IV (0.424-, 0.093-, 0.234 (P 0.001), and 0.141-fold (P 0.005), respectively). The mRNA level of EGFR increased in all grades I-II-III-IV 1.388, 5.452 (P 0.017), 4.624-, and 4.137-fold, respectively. The mRNA level of PTEN increased in grades I-II-III 1.802-, 1.702-, and 1.5-fold, respectively and decreased in grade IV (0.176-fold). The mRNA level of CD276 increased in all grades I-II-III-IV 1.8-, 5.756-(P 0.001), 10.303 (P 0.001), and 2.5-fold, respectively.
We determined similar findings for the previously reported PDK1, EGFR, PTEN, and CD276 gene expression levels. In contrast, SLC2A1 gene expression was downregulated remarkably, as reported in other tumor studies. These findings may be due to the unique nature of brain tumor tissues. Additionally, a decrease in PTEN gene expression was determined in grade IV brain tumors, including glioblastoma and meningioma. Although the size of the analyzed study group was limited, the gene expression results show similarities in behaviors of genes in cancer staging.
The aim of this study was to determine the expression levels of CDH1, FHIT, and TTPAL genes and to determine the genotype and allele frequencies of the IL7Rα gene polymorphism rs6897932 in patients ...with breast cancer.
The expression levels of genes and the distribution of the IL7Rα gene polymorphism rs6897932 were analyzed by real-time polymerase chain reaction.
No differences in genotype ratios or allele frequencies were observed between the 2 groups for the IL7Rα gene polymorphism rs6897932. The frequency of the IL7Rα rs6897932 T risk allele was found to be similar between breast cancer patients and controls. CDH1 messenger RNA (mRNA) levels decreased (0.714-fold and 0.834-fold, respectively), and TTPAL mRNA levels increased (2.675-fold P < .05 and 1.169-fold, respectively) in tumor tissues and peripheral blood samples. FHIT mRNA levels decreased (0.559-fold) in tumor tissue samples and increased (2.21-fold) in peripheral blood samples.
Our results are compatible with those reported in the literature. It can be suggested that the upregulation observed in the TTPAL gene might be a marker for breast cancer. The downregulation of CDH1 and FHIT gene expression has been validated in our study. An increase in the copy numbers of FHIT mRNA in blood samples and a decrease in the tumor samples can also be considered an abnormal condition.
Abstract
Mucopolysaccharidosis type IIIB (Sanfilippo's B; OMIM no.: 252920) is a lysosomal storage disorder caused by defective degradation of heparan sulfate. The enzyme that has decreased function ...in this disease is α-N acetylglucosaminidase. This enzyme is encoded by the
NAGLU
gene. A 9-year-old male patient was referred to us with speech disability, developmental delay, hepatomegaly, mild learning disability, and otitis media with effusion complaints. Whole exome sequencing (WES) was performed because of consanguinity between the parents of the patient and the lack of specific prediagnosis. As a result of the patient's WES analysis, a homozygous mutation was detected in the
NAGLU
gene. The leukocyte enzyme activity was then evaluated to confirm the diagnosis. Alpha-N acetylglucosaminidase deficiency was found. Alpha-N acetylglucosaminidase activity was 0.2 nmol/mLh. WES is a successful diagnostic method in the diagnosis of the mild clinical diseases with recessive inheritance. In addition, our case is a good example of genotype to phenotype diagnosis. Because in storage diseases, the diagnosis is made by leukocyte enzyme analysis first, and then the result is confirmed by gene analysis. The opposite situation occurred in our case.
Abstract only
e11092
Background: Due to advances in treatment modalities and palliative care patients with breast cancer live longer compared to the past and thus encounter an increased risk for ...secondary cancers. This study aims at finding the frequency of other solid cancers in a retrospective cohort. Methods: A search for the history of a non-breast solid tumor (NBST) among 1914 women admitted to our institute with stage I to IV breast cancer between 2006 – 2012 was conducted. Frequency of NBST according to temporal relation with breast cancer diagnosis was calculated Results: Overall 79 NBST and 75 patients (3.9 %) with another solid tumor were discovered. Of the patients 4 had more than one tumor. For these patients the median age at diagnosis was 55 (28 – 93), median follow-up time for breast cancer was 32 months (1 – 132). Post-menopausality was 60.8 %. The most common breast cancer histology was infiltrative ductal carcinoma (70.9 %). Of the 79 NBST, 34 (43.0 %) were diagnosed after breast cancer; 30 (38.0 %) before; and 15 (19.0 %) synchronously. Median time of diagnosis for NBST after breast cancer was 21 months (7 – 296). The most common malignancies were cancers of the ovary, thyroid and uterus (17.7, 15.2 and 11.4 %, respectively). Conclusions: The frequency of gynecological cancers and thyroid cancer along the course of breast cancer is high. Common environmental and genetic factors and may be involved. These patients should be followed closely
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