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Biomedical subjects

Unal Egeli

Publications and source records attributed to Unal Egeli.

16 recordsLinked to original sources
PubMed2006

Impact of novel PTEN mutations in Turkish patients with glioblastoma multiforme.

Glioblastoma multiforme (GBM) represents the most common and aggressive type of primary neoplasms of the central nervous system. The PTEN (phosphatase, tensin homologue, deleted on chromosome TEN; MIM # 601728) tumor suppressor gene has an essential biological role in the formation of glioblastomas. It is known that there are variations in genetic alterations in tumors that develop in patients with different ethnic backgrounds and because there is no study evaluating PTEN mutation in Turkish patients with GBM, we aimed to realize the present study. We investigated 62 GBM tumors for mutations of the PTEN gene using single strand conformational polymorphism (SSCP) method followed by DNA sequencing. As a result of our investigation, PTEN mutations were detected in 15 of 62 tumors (24.19%). Nine different sequence variants were identified: one novel promoter site mutation (5'UTR -9C-->T), one novel intronic mutation (IVS2-2delA), four novel point mutations (61A-->G, 105T-->G, 248C-->G, and 364C-->G), two novel frameshift mutations (213delC) and 378delGATA) and one previously reported global exonic transition type mutation (129G-->A). Since the majority of PTEN mutations identified in the present study are novel, we believe that these alterations may be specific to Turkish population. Furthermore, though no significant correlation was found between PTEN mutations and histopathological properties of GBM tumors, our findings indicate that localizations of mutations in PTEN gene may have an effect on clinical aggressiveness of GBM tumors.

Adult↗
PubMed2006

Assessment of molecular events in squamous and non-squamous cell lung carcinoma.

Although considerable knowledge exists on the tumor biology of lung cancer, there is still a need to assess molecular events for the clinical management of the disease. We studied the pattern of chromosomal imbalances in 45 non-small cell lung carcinomas (NSCLC) by comparative genomic hybridization (CGH) and correlated the results with clinicopathological features including immunohistochemical (IHC) expression of the epidermal growth factor receptor (EGFR). Twenty-one tumors were squamous cell carcinomas (SCC) and 24 non-squamous cell lung carcinomas (NSCC) comprising 9 adenocarcinomas (ADC), 9 large cell carcinomas (LCC), 4 sarcomatoid carcinomas and 2 adenosquamous carcinomas. The mean number of individual imbalances was 7.1 for SCC (mean gains, 3.8; mean losses, 3.4) and 6.4 for NSCC (mean gains, 4.5; mean losses, 1.9). Several individual imbalances correlated significantly with increasing number of imbalances, that were +1q, -3p, +3q, -5q, -8p, +8q, +7p, +12p, and +14q. Altogether, the most frequent imbalances were +3q (49%), +5p (49%), -5q (36%), +8q (29%), -8p (24%), -3p (22%), +7p (22%), +12p (22%), +14q (20%), +18p (20%), +1q (18%), and +7q (18%). Among these, +3q and +18p correlated significantly with SCC, and +5p and +14q with NSCC. Remarkably, overlapping imbalances included +3q26, +7p11 in SCC and +1q21, +3q24, +12p11, and +14q12 in NSCC. EGFR expression was higher in SCC than in NSCC and correlated with +3q in the entire series. In addition, +12p correlated significantly with disease progress with the exception of nodal involvement in NSCC as well as with disease progress, regardless of nodal involvement, in the entire series. In conclusion, the present study contributes to the molecular biological characterization of NSCLC histological subtypes and through evaluation of molecular events to the recently emergent focus on novel markers for lung cancer treatment.

Adult↗
PubMed2006

Meiotic segregation analysis of reciprocal translocations both in sperms and blastomeres.

Balanced chromosomal rearrangements could lead to unbalanced segregation gametes during meiosis. In this study, sperm flourescence in situ hybridization (FISH) analysis of meiotic segregation products of four reciprocal translocations; 46,XY,t(7;10)(q21;q22), 46,XY,t(15;17)(q11;p12), 46,XY,t(6;13)(p21.1;q32), and 46,XY,t(1;13)(q24;q10) are presented. In three out of these four cases with t(15;17), t(6;13), and t(1;13) additional blastomere FISH analyses are also provided. Multi-color FISH analysis was applied using diverse probe combinations specific for translocated chromosome segments. The average frequency of sperm nuclei bearing unbalanced products for t(7;10), t(15;17), t(6;13), and t(1;13) were 48.7%, 59.5%, 60.5%, and 62.9%, respectively. Frequencies of blastomeres comprising unbalanced products in cases with t(15;17), t(6;13), and t(1;13) were 80% (12 of 15), 60% (3 of 5), and 50% (2 of 4), respectively. Chi-square test analysis showed significant differences in the meiotic segregation patterns due to the distribution and numbers of the chiasmatas that could depend on the size of the translocated segments (P < 0.001). In conclusion, FISH analysis of sperm and blastomere for reciprocal translocation carriers effectively estimates the approximate risk of unbalanced products and this result might ensure valuable genetic counseling.

Blastomeres↗
PubMed2006

FISH investigation of 22q11.2 deletion in patients with immunodeficiency and/or cardiac abnormalities.

DiGeorge anomaly/velocardiofacial syndrome (DG/VCFS), called 22q11.2 deletion syndrome in general, is the most common chromosomal deletion syndrome found in humans. Typical facial features, palatal defects, conotruncal abnormalities of the heart, aplasia/hypoplasia of the parathyroid glands and of thymus are characteristics of this syndrome. Deletions of chromosome 22q11.2 (del22q11.2) are the leading causes of DG7VCFS. We report on a systematic search by fluorescence in situ hybridization (FISH) for deletions of chromosomes 22q11.2 in patients with a clinical suspicion or diagnosis of DG/VCFS. Using FISH we studied a series of 43 patients with suspected DG/VCFS. In this study, a total of 43 patients were investigated for the presence of a 22q11.2 deletion over a two-year period. Del22q11.2 was detected in 5 of the 43 patients tested. All patients with deletion had hypocalcemia, 80% had cardiac defects, 40% had facial dysmorphism, 40% had immunodeficiency , and 20% had otolaryngeal abnormalities. Chromosome 22q11.2 deletion is a relatively common condition and is readily diagnosed by FISH. We suggest that FISH analysis of 22q11.2 deletion should be performed in the presence of combined of hypocalcemia and congenital cardiac malformations, with or without any characteristics of the disease. This may facilitate an early diagnosis in such patients.

Child, Preschool↗
PubMed2005

Investigation of APC mutations in a Turkish familial adenomatous polyposis family by heterodublex analysis.

PURPOSE: Familial adenomatous polyposis is an autosomal dominant disease characterized by the presence of 100 or more colorectal adenomatous polyps. Mutations in the adenomatous polyposis coli gene are primarily responsible for the development of this disease. This study was designed to investigation of adenomatous polyposis coli (APC) gene mutations in members of familial adenomatous polyposis family to identify individuals at risk of the disease. METHODS: We examined one patient with familial adenomatous polyposis and 21 family members including one affected person from familial adenomatous polyposis and 20 nonsymptomatic persons. We studied E, D, F, and G segments of exon 15 of the adenomatous polyposis coli gene by heteroduplex analysis. RESULTS: We used silver staining method for staining. We found a mutation for five persons at segment F of exon 15 of the adenomatous polyposis coli gene. Two of them were affected by colorectal cancer, one of whom was the proband, and the other three were nonsymptomatic family members. The pathogenetic mutation was a T deletion at codon 1172, causing a frameshift in the adenomatous polyposis coli gene, as a result of the sequencing analysis of these cases. CONCLUSIONS: Investigation of adenomatous polyposis coli gene mutations is very important for the identification of genetic susceptibility to colorectal cancer and for the definition of tumor developing at an early stage. Furthermore, the identification of this mutation for the first time in a Turkish family will be useful to foster further studies on familial adenomatous polyposis in Turkey.

Adenomatous Polyposis Coli↗
PubMed2004

Comparison of genetic changes between interphase and metaphase nuclei in monitoring CML and APL treatment using DC-FISH technique.

In leukemias, the monitoring techniques on the response after the treatment have clinical importance for evaluating new therapeutic approaches and identifying the risk of relapse. In this study, genetic changes before and after chemotherapy in interphase and metaphase nuclei of bone morrow of adults with provisional diagnosis of leukemia were compared to understand the molecular characterization and pathogenesis of the leukemia for the classification of diagnosis and prognosis. We examined bone morrow cells of 47 chronic myeloid leukemia (CML) cases (29 of 47 at the time of diagnosis, 31 of 47 after chemotherapy) with the bcr/abl translocation probes and of 10 acute promyelocytic leukemia (APL) cases (7 of 10 at the time of diagnosis, 4 of 10 after chemotherapy) with the PML/RARalpha translocation probes by using dual color-flourescence in situ hybridization (DC-FISH). For each case, 400 interphase nuclei and 11 to 25 metaphases nuclei were analysed. The ratios of translocations before and after chemotherapy were compared between interphase and metaphase nuclei. After chemotherapy, though, translocations were detected in interphase nuclei of 29 of the 31 CML and 4 of the 4 APL cases, these translocations were determined in metaphase nuclei of only 14 of the 31 CML and 1 of the 4 APL cases with very low ratios (p < 0.01). The results showed that the rates of translocation positive interphase nuclei were higher than the rates of translocation positive metaphase nuclei (p < 0.01) after chemotherapy, so there may be some factors effecting proliferative activity of metaphase formation in leukemias.

Bone Marrow Cells↗
PubMed2003

Frequency of recombinant and nonrecombinant products of pericentric inversion of chromosome 1 in sperm nuclei of carrier: by FISH technique.

Meiotic segregation products of carriers with pericentric inversion are very important for assessing the risk of unbalanced forms and appropriate genetic counseling. We investigated the incidence of recombinant and nonrecombinant products of chromosome 1 with pericentric inversion, in the sperm nuclei of the carrier by using triple color fluorescence in situ hybridization (FISH). The centromere specific and telomere specific probes for chromosome 1 were used. In the segregation analysis, 1,636 sperm nuclei were analyzed; 82.5% of the sperms were including normal or inverted chromosome 1, and the dup(p)/del(q) and del(p)/dup(q) recombinant products in sperm nuclei of our carrier were 8.7 and 7.3%, respectively. The number of recombinant products may be dependent on the formation of an inversion loop, which the number of the formation of chiasmata results in the different number of normal/balanced and recombinant products. The use of FISH, using different probe combination, in sperm nuclei has proved to be an accurate approach to determine the meiotic segregation patterns and could help to better establish a reproductive prognosis and genetic counseling.

Cell Nucleus↗
PubMed2003

Esophageal atresia and tracheo-esophageal fistula in a patient with Digeorge syndrome.

DiGeorge Syndrome (DGS) is a congenital disorder that affects the thymus, parathyroid glands, and heart and brain. Thymus involvement in DGS may vary between absence/hypoplasia of thymus to various forms of reduced T cell function. TBX1 deficiency causes a number of distinct vascular and heart defects, suggesting multiple roles in cardiovascular development, specifically, formation and growth of the pharyngeal arch arteries, growth and septation of the outflow tract of the heart, interventricular septation, and conal alignment. Here the authors describe a case of DGS presenting with severe combined immunodeficiency, esophageal atresia, and tracheoesophageal fistula (TEF). DGS is an important differential diagnosis in TEF.

Abnormalities, Multiple↗
PubMed2003

An unusual metastatic site of laryngeal carcinoma: scapular muscles.

It is well known that in advanced cervical metastatic disease of head and neck squamous cell carcinoma, the incidence of distant metastasis is high. A case of distant metastasis to the scapular muscles from an uncontrolled cervical metastasis of laryngeal carcinoma is presented. Other unusual metastatic sites are reviewed and the possible mechanism of the spread is discussed.

Carcinoma, Squamous Cell↗
PubMed2002

Evaluation of relationship between chromosome 22 and p53 gene alterations and the subtype of meningiomas by the interphase-FISH technique.

In this study, we investigated the relationship between genetic alterations such as chromosome 22 aneuploidy and p53 gene deletion, and the pathological types of meningioma of typical and aggressive forms. Thirty-four meningiomas (23 typical and 11 aggressive) were examined by application of fluorescence in situ hybridization (FISH) with chromosome 22 specific alpha satellite probe and a combination of p53 locus specific and chromosome 17 centromere specific alpha satellite probes, to evaluate the chromosome 22 aneuploidy and gain or loss of p53 gene along with chromosome 17. The results showed that, although chromosome 22 aneuploidy was seen in 7 out of 23 typical (30.4%) and 4 out of 11 aggressive meningiomas (36.3%), no p53 deletion was detected in typical meningiomas, and p53 deletion was detected in 3 out of 11 aggressive meningiomas (1 atypical and 2 malignant), which had recurrence. There were no simultaneous occurrences of p53 gene deletions between typical and aggressive meningiomas. The present findings indicate that the loss of chromosome 22 may be involved with tumorogenesis of typical and aggressive meningiomas, while p53 gene deletions may be involved with malignant progression and recurrence in the aggressive meningiomas.

Adult↗
PubMed2002

Investigation of genetic susceptibility to non-small cell lung cancer by fragile site expression.

Fragile sites are non-staining gaps and breaks in specific points of chromosomes that are inducible by various culture conditions. Previous studies have shown that various clastogenic agents increase expression of fragile sites. In this study, the expression of common fragile sites induced by aphidicolin was evaluated on prometaphase chromosomes obtained from peripheral blood lymphocytes. Chromosomal aberrations and fragile site expression of 60 individuals, including 20 patients with non-small cell lung cancer (NSCLC), 20 of their clinically healthy family members, and 20 age-matched normal healthy controls without history of any cancer type were studied. Both the proportion of damaged cells (P < 0.001) and the mean number of gaps and breaks per cell (P < 0.001) were significantly higher in both the patients and relatives' groups when compared with the control group. However, they were insignificant when the patients were compared to their relatives (P > 0.05). We determined four aphidicolin type common fragile sites in our study. These sites in patients with NSCLC and relatives were the following: 1p21, 2q33, 3p14, and 16q23. In these fragile sites, 2q33, 3p14, and 16q23 sites were statistically significant when compared with control group (P < 0.001, P < 0.0005, and P < 0.05, respectively). Consequently, we believe that fragile site studies may be helpful to detection of cancer risk.

Adolescent↗
PubMed2002

Determination of allelic deletion of multiple endocrine neoplasm type 1 (MEN1) gene in acute myeloid leukemia (AML) by application of FISH-TSA technique.

We have used the single and dual color fluorescence in situ hybridization (FISH) technique combined with a new detection system, tyramide signal amplification (TSA), by using the multiple endocrine neoplasm type 1 (MEN1) gene and chromosome 11 specific alpha satellite DNA probes for the study of the allelic deletion of the MEN1 gene. The MEN1 gene is a new tumor suppressor gene and has been recently cloned on chromosome 11q13. FISH combined with the TSA detection system was performed on bone marrow interphase nuclei of 22 patients with acute myeloid leukemia (AML). The FISH-TSA analysis revealed the mono allelic deletion of the MEN1 gene in 4 out of 22 patients (18.18%), 2 of 9 AML-M2 patients (22.2%), 1 of 6 AML-M4 patients (16.6%), and 1 of 4 AML-M5 patients (25.0%). Our study indicates that allelic deletion of the MEN1 gene is not a major cause or a primary event in tumorigenesis of AML, although the long arm (q13 region) of chromosome 11 involves a chromosomal rearrangement in AML.

Adolescent↗
PubMed2002

Investigation of genotoxic effect of taxol plus radiation on mice bone marrow cells.

In this study, we investigated the genotoxic effect of taxol, radiation, or taxol plus radiation on highly proliferative normal tissue-bone marrow cells of Swiss albino mice. Swiss-albino mice, 3-4 months old, were used in this study. Taxol was administered bolus intravenously through the tail vein. Radiation was given by using a linear accelerator. There were four treatment categories, which had a total of 34 groups. Each group consisted of five animals. The first was the control category that had one group (n = 5). The second treatment category was taxol alone, which had three groups as per taxol dose alone (n = 15). The third treatment category was radiation alone, which had three groups as per the radiation dose (n = 15). The fourth treatment category was taxol plus radiation, which had 27 groups as per combined radiation dose plus taxol dose concentration and as per pre-treatment timing sequence of taxol before radiation (n = 135). Mice were sacrificed 24 h after taxol or radiation or combined administration using ether anesthesia. The cells were then dropped on two labeled slides, flamed, air dried, and stained in 7% Giemsa; 20-30 well-spread mitotic metaphases were analyzed for each animal; the cells with chromosome breaks, acentric fragments, and rearrangements were evaluated on x1,000 magnification with light microscope (Zeiss axioplan). The mitotic index was determined by counting the number of mitotic cells among 1,000 cells per animal. Differences between groups were evaluated with Student's t-test statistically. Taxol caused a dose-dependent increase in chromosomal aberrations (P = 0.027). Similarly, radiation caused a dose-dependent increase in chromosomal aberrations (P = 0.003) and decreased mitotic index (P = 0.002). In combination, there were a small enhancements at the 40 mg/kg taxol dose level and at 0.25 and 0.5 Gy radiation doses in the 48 h group. However, an increase in chromosomal aberrations was observed after 48 hours of taxol exposure when compared 12 or 24 h of taxol exposure (P = 0.001 and P = 0.019). These findings suggest that taxol at the high doses with low dose radiation caused radiosensitizing effect in bone marrow cells. Forty-eight-hour pretreatment of taxol exposure followed by radiation caused significant induction of chromosomal aberrations and a reduction of mitotic index when compared to other taxol timing sequence.

Animals↗
PubMed2002

Superior mesenteric artery aneurysm.

A 38-year old woman with mid-epigastric pain, diarrhea, and weight loss, underwent resection of a superior mesenteric artery aneurysm and primary repair of the artery. Pathological examination showed degenerative atherosclerotic changes, marked medial and intimal thickening, and vegetations. Microbiological studies demonstrated Streptococcus viridans as the infecting organism of this mycotic aneurysm. The patient made a good recovery and remained well after 3 years.

Adult↗
PubMedDate not supplied

Novel germline BRCA1 and BRCA2 mutations in Turkish women with breast and/or ovarian cancer and their relatives.

BRCA1 and BRCA2 gene mutations in patients with breast and/or ovarian cancer have been not characterized in the Turkish population until now. A total of 87 female subjects from two sets of families (38 families total) provided blood samples from which DNA was extracted. All coding exons of the BRCA1 and BRCA2 genes were screened for mutations with heteroduplex analysis and sequencing. Fourteen of the families (49 subjects comprising 17 patients and 32 unaffected relatives) had at least 2 women affected by breast and/or ovarian cancer. The other 24 families (38 subjects unaffected by breast and/or ovarian cancer) also had a history of these 2 forms of cancer. Six different sequence variants were detected: one previously described truncating mutation (5382insC) and one novel polymorphism (3663C-->A) in BRCA1, and 2 novel truncating mutations (9329insC and 9934insG), one novel intronic polymorphism 7069+41(TTTT-->AAAG), and one previously reported global polymorphism (1093A-->C) in BRCA2. BRCAPRO software was used for analysis, and the results showed that the level of risk for both breast and ovarian cancer increased with age in women who carried the mutation. In conclusion, these findings contribute significantly to what currently is known about the types and impact of germline BRCA1 and BRCA2 mutations in Turkish women.

Adult↗