Erdal Tunç

The genotoxic effect of nicotine on chromosomes of human fetal cells: The first report described as an important study

Context: Recent studies have suggested a direct contribution of nicotine − the addictive component of tobacco and tobacco smoke − to human carcinogenesis, and it remains the most common harmful substance to which pregnant women are exposed. Also, it has deleterious effects on the fetus. The sperm of smoking fathers and newborns of smoking mothers have elevated frequencies of chromosome translocations and DNA strand breaks. Objective: We tried to understand the genotoxic effect of nicotine in pregnancies of active or passive smoking mothers. For this reason, we provide the evidence that nicotine exposure in vitro has detrimental effects on fetal cells. Materials and methods: We examined the effect of nicotine sulphate on amniotic cells by designing an experimental setting consisting fetal cells grown in nicotine containing medium (25 ng/mL) in study group and fetal cells grown in control medium, which did not contain nicotine. Results: According to our findings, there is a significant difference of chromosomal aberrations (CAs) between nicotine containing medium grown cells and control medium grown cells, determined by the χ2 test (P <0.001). We found CAs in 21.5% of cells analyzed. The 19.4% of the all cells had numerical aberrations. Chromosomes 21, 22, 8, 15 and 20 related numerical abnormalities were found to be the most frequent numerical abnormalities. Conclusion: Results of this study confirm that the nicotine leads to significant direct genotoxic effects in human fetal cells in vitro. We speculate that there is an association between prenatal exposure to cigarette smoke and in utero aneuploidies.

Chromosomal analyses of 1510 couples who have experienced recurrent spontaneous abortions

In this retrospective study, karyotype results of 1510 couples with a history of recurrent spontaneous abortion were evaluated. The study was conducted at Balcalı Hospital in Adana region of Turkey. For all cases, peripheral blood lymphocytes were cultured for chromosome study using the standard method. Chromosome aberrations were detected in 62 couples (4.1% of all couples). At an individual level, chromosome aberrations were found in a total of 65 cases (41 females and 24 male cases), with structural chromosomal aberrations in 58 cases including balanced translocations in 30 cases, Robertsonian translocations in 12 cases, deletions in seven cases, inversions in nine cases and numerical chromosome aberrations in seven cases. The results of the study indicated that structural aberrations, particularly translocations, were the most common type of aberration observed among couples who had experienced recurrent spontaneous abortions and that these couples might benefit from cytogenetic analyses.

Genetic alterations of chromosomes, p53 and p16 genes in low- and high-grade bladder cancer

A majority of patients with bladder cancer present with superficial disease and subsequently, some patients show progression to muscle invasive or metastatic disease. Bladder cancer has a complex genetic process and identification of the genetic alterations which occur during progression may lead to the understanding of the nature of the disease and provide the possibility of early treatment. The aim of the present study was to compare the structural and numerical chromosomal differences and changes in the p16 and p53 genes between low-grade (LG) and high-grade (HG) bladder cancer (BC) using cytogenetic and molecular cytogenetic methods. Between March 2009 and March 2010, cytogenetic analyses were carried out on tumor and blood samples in 34 patients with transitional cell type BC, and on blood samples of 34 healthy patients as a control group. Fluorescence in situ hybridization probes for the p16 and p53 genes were also used to screen the alterations in these genes in 32 patients with BC. The patients were divided into two groups (LG and HG) and the findings were compared. A total of 11 (32.3%) patients exhibited LGBC, 22 (64.7%) exhibited HGBC and one (3%) patient exhibited carcinoma in situ. There were no differences between the LGBC and HGBC groups according to the number of chromosomal aberrations (P=0.714); however, differences between alterations of the p16 and p53 genes were significant (P=0.002 and P=0.039). Almost all structural abnormalities were found to be located to the 1q21, 1q32, 3p21 and 5q31 regions in patients with HG tumors. In conclusion, the p16 and p53 genes were altered more prominently in patients with HG tumors compared with LG tumors. The structural abnormalities in the 1q21, 1q32, 3p21 and 5q31 regions were observed more frequently in patients with HG tumors. These regions may play significant roles in the progression of BC, but further studies are required to find candidate genes for a panel of BC.

International evaluation of unrecognizably uglifying human faces in late and severe secondary hyperparathyroidism in chronic kidney disease. Sagliker syndrome. A unique catastrophic entity, cytogenetic studies for chromosomal abnormalities, calcium-sensing receptor gene and GNAS1 mutations. Striking and promising missense mutations on the GNAS1 gene exons 1, 4, 10, 4.

Hypotheses explaining pathogenesis of secondary hyperparathyroidism (SH) in late and severe CKD as a unique entity called Sagliker syndrome (SS) are still unclear. This international study contains 60 patients from Turkey, India, Malaysia, China, Romania, Egypt, Tunisia, Taiwan, Mexico, Algeria, Poland, Russia, and Iran. We examined patients and first degree relatives for cytogenetic chromosomal abnormalities, calcium sensing receptor (Ca SR) genes in exons 2 and 3 abnormalities and GNAS1 genes mutations in exons 1, 4, 5, 7, 10, 13. Our syndrome could be a new syndrome in between SH, CKD, and hereditary bone dystrophies. We could not find chromosomal abnormalities in cytogenetics and on Ca SR gene exons 2 and 3. Interestingly, we did find promising missense mutations on the GNAS1 gene exons 1, 4, 10, 4. We finally thought that those catastrophic bone diseases were severe SH and its late treatments due to monetary deficiencies and iatrogenic mistreatments not started as early as possible. This was a sine qua non humanity task. Those brand new striking GNAS1 genes missense mutations have to be considered from now on for the genesis of SS.

Identification of chromosome abnormalities in screening of a family with manic depression and psoriasis: Predisposition to aneuploidy

Cytogenetic analysis is an important stage in understanding the genetic background of manic depression (MD), and may provide a valuable clue to the identification of target loci and successful search for major genes. In order to identify chromosomal regions we aimed to detect the relationships between chromosomal aberrations (CAs) and immunological markers in a family with MD and psoriasis. We used the cell cultivation and conventional G-banding. We found predominantly numerical aberrations. The most common aneuploidy was chromosome 8, followed by chromosome 22, 21, 15, X and Y. However, structural aberrations consisted of duplications, deletions, translocations and breaks, with a focus on: loci on del(1)(q12-q23), del(1)(q21.1-q24), del(1)(q21.1-q23), del(10)(p11.2-pter), der(2)t(2;4)(p25;p12), t(2;22)(p14;p13), t(19;Y)? and dup(10)(q26). The susceptibility genes of MD or psoriasis may be located on these loci. Numerical sex CAs included 4(5.8%) with 45,X, 3(4.3%) with 47,XXY, and 4(5.8%) with structural chromosome X; del(X)(q13); del(X)(p11-pter) del(X)(q21.3) and inv(Y)(q11.2). We also conducted an immunological study. According results of this study, the percentage of CD2+, CD4+ and CD8+ lymphocytes of the father were significantly higher, whereas CD4+ lymphocytes were decreased in the mother, when compared the healthy persons. The percentage of CD4 level of the son was decreased, whereas CD8+ lymphocytes were higher. The CD4/CD8 ratio of the father and the son was found to be significantly high. These results may suggest that MD and psoriasis have a significant impact on both genetic and immunological parameters.

Phenotypic correlations in a patient with ring chromosome 22.

Ring chromosome 22, a rare cytogenetic anomaly, has been described in over 60 cases in the medical literature. The aim of this report was to present a case carrying ring chromosome 22, and her family. It is a case report of a patient presented at Medical Faculty of Çukurova University in Turkey. An 8-year-old girl with ring chromosome 22 and her family were evaluated cytogenetically and clinically. A chromosome analysis of the proband revealed a de novo 46, XX, r(22)(p11.2;q13) karyotype. Our subject demonstrated the prominent features of this syndrome including profound mental retardation, language impairment, dysmorphic features, lack of speech, hyperactivity, and behavioral disorders. There is lack of consistency between the physical abnormalities that we observed in our subject and those observed for such patients in the literature. The wide range of manifestations observed in patients with this cytogenetic alteration is probably due to size differences in the deleted region.

Frequency and Types of Chromosomal Abnormalities in Turkish Women with Amenorrhea

STUDY OBJECTIVE To estimate the frequency and the type of chromosomal abnormalities (CA) in patients with primary (PA) and secondary amenorrhea (SA). DESIGN This retrospective study was comprised of patients had been referred to our laboratory between 1990 to 2008 and designed as original article. SETTING Medical Faculty of Cukurova University in Turkey. PARTICIPANTS Chromosomal analysis was carried out on 393 patients with PA and SA that were referred to Cytogenetic laboratory of Medical Biology and Genetic Department, Faculty of Medicine, Çukurova University. INTERVENTIONS Lymphocyte culturing depended karyotyping. MAIN OUTCOME MEASURES Standard lymphocyte culturing procedure and karyotyping was performed to all samples. RESULTS PA and SA were identified in 393 patients. The karyotype was normal in 337 cases (85.8%) and abnormal in 56 (14.2%) patients. CAs were found in 54 (13.7%) and 2 (0.5%) of women with PA and SA, respectively. Females carrying rearrangements between autosomal and sex chromosomes were detected in 2% (8/393). The numerical abnormalities of the X chromosome were detected in 39.3% (22/56) (monosomy and mosaic). Structural abnormalities of the X and the other chromosomes were detected in 25.5% (13 of 56). Structural mosaicism of X chromosome was found in 5.4% (3 of 56). Male karyotype (46, XY) was found in 33.9% (19/56). The most frequently detected abnormality were X chromosome monosomies or mosaics. CONCLUSIONS Our study revealed that some causes of amenorrhea could be due to CAs. Therefore, cytogenetic study should be important test in the evaluation of patients with PA or SA. The most common abnormality seen is 45,X karyotype (monosomy X/Turner Syndrome) and its variants.

Chromosome imbalances and alterations in the p53 gene in uterine myomas from the same family members: familial leiomyomatosis in Turkey.

Uterine leiomyomas (UL) are extremely common neoplasms in women of reproductive age, and are associated with a variety of characteristic choromosomal aberrations (CAs). The p53 gene has been reported to play a crucial role in suppressing the growth of a variety of cancer cells. Therefore, the present study investigated the effects of CAs and the p53 gene on ULs. We performed cytogenetic analysis by G-banding in 10 cases undergoing myomectomy or hysterectomy. Fluorescence in situ hybridization (FISH) with a p53 gene probe was also used on interphase nuclei to screen for deletions. In patients, CAs were found in 23.4% of 500 cells analysed, significantly more frequent than in the control group (p<0.001). In the patients, 76% of the abnormalities were structural aberrations (deletions, translocations and breaks), and only 24% were numerical. Deletions were the most common structural aberration observed in CAs. Among these CAs, specific changes in five loci 1q11, 1q42, 2p23, 5q31 and Xp22 have been found in our patients and these changes were not reported previously in UL. The chromosome breaks were more frequent in cases, from high to low, 1, 2, 6, 9, 3, 5, 10 and 12. Chromosome 22, X, 3, 17 and 18 aneuploidy was observed to be the most frequent among all numerical aberrations. We observed a low frequency of p53 losses (2-11%) in our cases. The increased incidence of autosomal deletions, translocations, chromatid breaks and aneuploidy, could contribute to the progression of the disease along with other chromosomal alterations.

Genetic polymorphisms of estrogen receptor alpha and catechol-O-methyltransferase genes in Turkish patients with familial prostate carcinoma.

OBJECTIVES: Estrogen is one of the most crucial hormones participating in the proliferation and carcinogenesis of the prostate glands. Genetic polymorphisms in the estrogen metabolism pathway might be involved in the risk of prostate carcinoma development. We evaluated the association between genetic polymorphisms in estrogen receptor alpha (ESR1) and catechol-O-methyltransferase (COMT) genes and the risk of developing familial prostate carcinoma. MATERIALS AND METHODS: In this study, 34 cases with prostate carcinoma whose first-degree relatives had prostate carcinoma and 30 healthy age-matched male controls were enrolled. The genotypes of ESR1 and COMT genes were analyzed employing polymerase chain reaction-restriction fragment length polymorphism method. 34 cases with prostate carcinoma, whose first degree relatives had prostate carcinoma and 14 age-matched male controls were enrolled to analyze the genotype of these two genes. RESULTS: Among control patients, the ESR1 PvuII genotypes of C/C, C/T and T/T were observed in 37%, 26% and 37%, respectively, whereas the C/C, C/T and T/T genotypes were observed in 18%, 41% and 41% of case patients, respectively. Among controls, the ESR1 PvuII allele frequencies of C and T were equally observed, whereas the C and T allele frequencies were observed in 38% and 62% of patients, respectively. Among ESR1 PvuII genotypes there were not any significant difference in terms of genotype (P = 0.199) and allele (P = 0.181) frequencies. Among controls, the ESR1 XbaI genotypes of G/G, G/A and A/A were observed in 33%, 37% and 33%, respectively, whereas the G/G, G/A and A/A genotypes were observed in 12%, 47% and 41% of patients, respectively. Among controls, the ESR1 XbaI allele frequencies of A and G were observed equally, respectively, whereas the A and G frequencies were observed in 65% and 35% of patients, respectively. Among ESR1 Χ baI, there was not any significant difference in terms of genotype (P = 0.111) and allele (P = 0.093) frequencies. But the C/C genotype of the PvuII site and G/G genotype of the XbaI site in the ESR1 gene were associated significantly with the risk of developing prostate carcinoma. The G/G, G/A and A/A genotypes of the COMT gene were observed in 50%, 29% and 21% of control patients and in 53%, 21% and 26% of case patients, respectively. The A and G allele frequencies of the COMT gene were observed in 36.7%, 63.3% of control patients and in 36.8%, 63.2% of case patients, respectively. In COMT gene, there was not any significant difference in terms of genotype (P = 0.843) and allele (P = 0.991) frequencies. But the G/A genotype of the COMT gene had a weak tendency toward increased risk. CONCLUSION: Polymorphisms of ESR1 gene in the estrogen metabolism pathway were associated significantly with familial prostate carcinoma risk. Single nucleotide polymorphisms of low-penetrance genes are targets for understanding the genetic susceptibility of familial prostate carcinoma.

Diagnosis of chromosomal abnormalities in a patient with thanatophoric dysplasia (TD) type I: The first report describing an important association between cytogenetic findings and TD

Summary Background: Thanatophoric dysplasia (TD) is the most lethal and most severe type of dysplasia. It has distinct features, the most important of which is short tubular bones and short ribs with platyspondyly, allowing a precise radiologic and prenatal ultrasonographic diagnosis. It has been reported to be caused by mutations in the FGFR3 gene, but exactly how cytogenetic abnormalities might lead to TD is unclear. Case Report: We report a case of TD with different prenatal sonographic features compatible with the classification of type I. In the result of cytogenetic examination, we found de novo CAs in 28% of cells analyzed from the affected infant; 75% of the abnormalities were numerical, and of those, 25% were structural aberrations; 21% of cells revealed predominantly numerical aberrations. Monosomy 18, 21 and 22 was observed in 4% of cells, monosomy 20 in 2%, and monosomy 7, 8, 14, 17 and 19 in 1%. Structural changes were observed in 7% of cells. Conclusions: It appears that these chromosomes may be preferentially involved in and important for TD development.