BRCA, infertility, and fertility preservation: a review for counseling.

BRCA mutations as a triggering factor in breast cancer have been reported to result in fertility problems and oocyte aging in young patients with cancer diagnosis. These patients are concerned about fertility problems and family planning before undergoing treatment modalities that may result in infertility. In this review, we conducted analysis of the literature on the association between BRCA mutations and infertility, possible fertility preservation options, and their safety and tried to gather results from different disciplines and points of view on the matter. Our aim is to provide a general summary of recent studies to provide further insight on the matter for counseling BRCA mutation carriers on fertility preservation methods and their implications.

Clinical and molecular evaluation of MEFV gene variants in the Turkish population: a study by the National Genetics Consortium.

Familial Mediterranean fever (FMF) is a monogenic autoinflammatory disorder with recurrent fever, abdominal pain, serositis, articular manifestations, erysipelas-like erythema, and renal complications as its main features. Caused by the mutations in the MEditerranean FeVer (MEFV) gene, it mainly affects people of Mediterranean descent with a higher incidence in the Turkish, Jewish, Arabic, and Armenian populations. As our understanding of FMF improves, it becomes clearer that we are facing with a more complex picture of FMF with respect to its pathogenesis, penetrance, variant type (gain-of-function vs. loss-of-function), and inheritance. In this study, MEFV gene analysis results and clinical findings of 27,504 patients from 35 universities and institutions in Turkey and Northern Cyprus are combined in an effort to provide a better insight into the genotype-phenotype correlation and how a specific variant contributes to certain clinical findings in FMF patients. Our results may help better understand this complex disease and how the genotype may sometimes contribute to phenotype. Unlike many studies in the literature, our study investigated a broader symptomatic spectrum and the relationship between the genotype and phenotype data. In this sense, we aimed to guide all clinicians and academicians who work in this field to better establish a comprehensive data set for the patients. One of the biggest messages of our study is that lack of uniformity in some clinical and demographic data of participants may become an obstacle in approaching FMF patients and understanding this complex disease.

Comparison of diagnostic criteria for children with familial Mediterranean fever.

Familial Mediterranean fever (FMF) is an autoinflammatory disease characterized by recurrent attacks of fever and serositis. Diagnosis is made according to clinical findings and supported by genetic analysis. The most commonly used adult diagnostic criteria are the Tel-Hashomer criteria. Pediatric criteria for FMF diagnosis were described in 2009, but their reliability should be supported by additional reports. In this study, we aimed to compare the pediatric criteria and the Tel-Hashomer and 2019 Eurofever/PRINTO classification criteria using our FMF cohort. A total of 113 patients diagnosed with FMF were included. Demographic features and laboratory findings were retrospectively collected from the patients' files. The patients were evaluated with the Tel-Hashomer, pediatric and Eurofever/PRINTO classification criteria. At least two of five new pediatric criteria were as sensitive (89%) and specific (85%) as the Tel-Hashomer criteria (sensitivity 70%, specificity 96%). We also evaluated the Eurofever/PRINTO classification criteria using our cohort and found a sensitivity of 94% and specificity of 91%.   Conclusion: Using pediatric criteria for the diagnosis of FMF in children is a feasible and simple approach that can diagnose the disease based on at least two criteria. Therefore, our study supports the use of pediatric criteria in FMF diagnosis of children. Our results also confirm that the Eurofever/PRINTO classification criteria can be successfully applied for the diagnosis of FMF due to their high sensitivity (94%) and specificity (91%). What is Known: • The FMF diagnosis is made according clinical findings and supported by genetic analysis. • The use of adult diagnostic criteria in pediatric FMF patients is controversial since classical clinical presentation is often absent in children. What is New: • Our study supports both the use of pediatric criteria and Eurofever/PRINTO classification criteria in clinical practice.

Causative Mutations and Mechanism of Androgenetic Hydatidiform Moles.

Androgenetic complete hydatidiform moles are human pregnancies with no embryos and affect 1 in every 1,400 pregnancies. They have mostly androgenetic monospermic genomes with all the chromosomes originating from a haploid sperm and no maternal chromosomes. Androgenetic complete hydatidiform moles were described in 1977, but how they occur has remained an open question. We identified bi-allelic deleterious mutations in MEI1, TOP6BL/C11orf80, and REC114, with roles in meiotic double-strand breaks formation in women with recurrent androgenetic complete hydatidiform moles. We investigated the occurrence of androgenesis in Mei1-deficient female mice and discovered that 8% of their oocytes lose all their chromosomes by extruding them with the spindles into the first polar body. We demonstrate that Mei1-/- oocytes are capable of fertilization and 5% produce androgenetic zygotes. Thus, we uncover a meiotic abnormality in mammals and a mechanism for the genesis of androgenetic zygotes that is the extrusion of all maternal chromosomes and their spindles into the first polar body.

Evaluation of silent information regulator T (SIRT) 1 and Forkhead Box O (FOXO) transcription factor 1 and 3a genes in glaucoma.

Analysis of the reactive oxygen species (ROS)-detoxifying biomarkers may elucidate the mitochondrial dysfunction in glaucoma pathogenesis. Therefore, we purposed to investigate the effects of ROS-detoxifying molecules including Silent Information Regulator T1 (SIRT1) and Forkhead Box O 1 (FOXO1) and 3a (FOXO3a) transcription factors in patients with glaucoma. Our analyses included 20 eyes from patients with primary open-angle glaucoma (POAG) and 20 eyes from patients with pseudoexfoliation glaucoma (PXG) who were scheduled for trabeculectomy. After extraction of total RNA from trabecular meshwork tissue, we compared the levels of SIRT1, FOXO1and FOXO3a genes in the oxidative pathway with the level of glyceraldehyde-3 phosphate dehydrogenase (GAPDH), the reference gene, using real-time polymerase chain reaction. Relative gene expression was calculated using the threshold cycle (2-ΔΔCT) method. We observed similarly reduced expression levels of SIRT1, FOXO1, and FOXO3a genes versus GAPDH among patient groups (p = 0.40; p = 0.56; p = 0.35, respectively). This is the first study to identify the role of SIRT1 and FOXOs in human TM with glaucoma. Relative expression levels of SIRT1, FOXO1, and FOXO3a genes versus a control gene (GAPDH) were decreased in POAG and PXG groups. Our results show that SIRT1and FOXOs (1-3a) deserve special attention in the pathogenesis of glaucoma.

Corchorus olitorius and Urtica pilulifera extracts alleviate copper induced oxidative damage and genotoxicity in tomato.

Copper cause oxidative damage in plant cells, and plant extracts are the sources of free radical scavengers. We tested the hypothesis that whether Corchorus olitorius (jute) and Urtica pilulifera (Roman nettle) seed extract treatments of germinated seeds affect copper induced oxidative and genotoxic damage or antioxidant response in tomato. Seedlings were exposed to toxic copper concentration (30 ppm) for 7 days. In one experimental group (treatment 1), extract (100 µg mL-1) was added to media. In the other group (treatment 2), tomato seeds were pre-soaked by the extract (100 µg mL-1) prior to germination and copper application. Malondialdehyde and endogenous H2O2 levels in the groups treated with extract and copper were significantly lower than that of the untreated groups. Pre-soaking seeds with the nettle extract solution significantly enhanced catalase activity under unstressed condition. Jute treatment also enhanced catalase activity under copper stress. Ascorbate peroxidase activity remained at unstressed level in copper treated groups. Extract treatments significantly decreased copper induced DNA damage in root nuclei. Jute seed extract contained salicylic acid and quercetin which can be correlated with the evoked effects. We demonstrated protective effect of plant extract treatments against copper stress of tomato seedlings prior to germination or during seedling development.

Effects of silymarin and silymarin-doxorubicin applications on telomerase activity of human hepatocellular carcinoma cell line HepG2.

PURPOSE: Hepatocellular carcinoma (HCC) is resistant to conventional chemotherapeutics such as doxorubicin. Milk thistle extract, or its active constituent silymarin has been used by cancer patients as an alternative and complementary agent. Telomerase activation is one of the initial events of HCC. In this study, we applied doxorubicin and silymarin for 72 hrs in order to test individual and combined effect of the agents on telomerase activity. METHODS: The effects of doxorubicin, silymarin, and their combination on the proliferation of HepG2 cell line were tested by MTT assay, and Checkerboard micro plate method was applied to define the nature of doxorubicin and silymarin interactions on the cells. Lipid peroxidations were assessed by thiobarbituric acid reactive substance (TBARS) level. Telomerase activity was determined according to the telomeric repeat amplification protocol (TRAP). Untreated cells were used as control group. RESULTS: Doxorubicin-silymarin combination had indifferent antiproliferative effects on HepG2 cells. Telomerase activity of the cells incubated with IC50 of doxorubicin and silymarin decreased to 72% (p<0.05). IC50 combinations of doxorubicin and silymarin caused 70% (p<0.05) reduction. All treatments except for the 1/2IC50 of silymarin caused significant increase in lipid peroxidation levels when compared to controls. TBARS levels did not significantly increase when doxorubicin and silymarin were applied in combination, which is in concordance with the indifferent drug interaction. CONCLUSION: IC50 of both doxorubicin and silymarin alone and in combination inhibited telomerase activity. Mechanism of inhibition may be elucidated by further molecular studies.

Fractalkine receptor polymorphism and chronic tonsillitis.

The objective of this study is to examine whether there is an association of fractalkine gene receptor polymorphisms with chronic tonsillitis. This is a cross-sectional study in the setting of a tertiary referral center. The study group included 79 patients with chronic tonsillitis and 76 controls without history of chronic tonsillitis. Genotypes were identified by restriction fragment length polymorphism analyses after polymerase chain reaction. c.745G>A (V249I) single nucleotide polymorphism and the frequencies of the G and A alleles did not differ in the patient and control groups (p = 0.363; p = 0.743, respectively). c.839C>T (T280M) single nucleotide polymorphism was found to be higher in controls than in the patients with chronic tonsillitis (p < 0.001). Consistent with this result, T allele frequency was higher in controls than in the patients with chronic tonsillitis (p < 0.001). In this study, we suggested that fractalkine gene receptor c.839C>T (T280M) single nucleotide polymorphism could be associated with a reduced risk of chronic tonsillitis.

beta-Adrenoreceptor antagonists reduce cancer cell proliferation, invasion, and migration.

CONTEXT: Propranolol, atenolol, and ICI118,551 are non-selective ß-adrenergic receptor (AR), ß1-AR, and ß2-AR antagonists, respectively. OBJECTIVE: We investigated the efficacy of propranolol, atenolol, and ICI118,551 on proliferation, migration, and invasion of non-stimulated breast (MCF7), colon (HT-29), and hepatocellular (HepG2) cancer cells. MATERIALS AND METHODS: ß-AR expression profiling of cells was performed by real time PCR. Cell proliferation was determined by MTT. Boyden chamber and scratch assays were performed to evaluate invasion and migration. RESULTS AND DISCUSSION: All cell lines expressed ß-ARs. ICI118,551 was the most cytotoxic, whereas atenolol was the least effective ß-AR antagonist for 24, 48, and 72 h. Cell invasion was inhibited by ICI118,551 (45, 46, and 50% for MCF7, HT29, and HepG2, respectively) and propranolol (72, 65, and 90% for MCF7, HT29, and HepG2, respectively). Propranolol, atenolol, and ICI118,551 reduced migration of MCF7, HT-29, and HepG2 cells to varying extents depending on the application concentration and duration. Propranolol and atenolol reduced migration of MCF7 and HT-29 in a concentration-dependent manner, whereas migration of these cells decreased after 48 and 72 h of ICI118,551 applications. CONCLUSION: Beta2-AR antagonist seemed to be the most cytotoxic ß-blocker on non-stimulated cancer cells. Propranolol and ICI118,551 were more effective than atenolol in inhibiting invasion and migration of non-stimulated MCF7 and HT-29 cells; ICI118,551 being the most potent. Concordantly, ß2-selective blockage seemed to be more effective for non-stimulated cells. Effect of the selective ß-AR antagonists showed variation depending on the concentration, incubation time, and histological origin of cells.

Blastoid variant mantle cell lymphoma with complex karyotype including 11q duplication.

We describe a case of blastoid mantle cell lymphoma with a complex karyotype. The blastoid variant is a rare type of non-Hodgkin lymphoma exhibiting an aggressive clinical course. Mantle cell lymphoma is a distinct entity of mature B-cell neoplasms genetically characterized by the presence of t(11;14). In the present case, conventional analysis revealed structural abnormalities of chromosomes 2, 4, 6, 10, 13, and 19, along with 3 additional marker chromosomes. The derivative 1 chromosome determined in the case was a result of t(1p;11q). Our interesting finding was the presence of a different translocation between 11q and chromosome 1 in addition to t(11;14). Thus, the resulting 11q duplication was believed to additionally increase the enhanced expression of cyclin D1 gene, which is responsible in the pathogenesis of the disease. Fluorescence in situ hybridization method by the t(11;14) probe revealed clonal numerical abnormalities of chromosomes 11 and 14 in some cells. The detection of multiple abnormalities explains the bad prognosis in the present case. On the basis of our findings, we can easily conclude that results of cytogenetic analyses of similar mantle cell lymphoma patients would provide clues about new responsible gene regions and disease prognosis. In conclusion, it has been suggested that the presence of multiple chromosomal aberrations in addition to the specific t(11;14) may have a negative impact on clinical course and survival rate.

High-antibacterial activity of Urtica spp. seed extracts on food and plant pathogenic bacteria.

The aim of this study was to comparatively evaluate antibacterial activities of methanol (MetOH) and aqueous (dw) leaf (L), root (R) and seed (S) extracts of Urtica dioica L. (Ud; stinging nettle) and Urtica pilulifera L. (Up; Roman nettle) on both food- and plant-borne pathogens, with total phenolic contents and DPPH radical scavenging activities (DRSA). MetOH extracts of leaves and roots of U. dioica had the highest DRSA. Extracts with high antibacterial activity were in the order Up-LMetOH (13/16) > Ud-SMetOH (11/16) > Up-SMetOH (9/16). Results obtained with Up-SMetOH against food spoiling Bacillus pumilus, Shigella spp. and Enterococcus gallinarum with minimum inhibitory concentrations (MICs) in 128-1024 µg/ml range seem to be promising. Up-SMetOH also exerted strong inhibition against Clavibacter michiganensis with a considerably low MIC (32 µg/ml). Ud-SMetOH and Up-LMetOH were also effective against C. michiganensis (MIC = 256 and 1024 µg/ml, respectively). Ud-SMetOH and Ud-RMetOH had also antimicrobial activity against Xanthomonas vesicatoria (MIC = 512 and 1024 µg/ml, respectively). Results presented here demonstrate high-antibacterial activity of U. pilulifera extracts and U. dioica seed extract against phytopathogens for the first time, and provide the most comprehensive data on the antibacterial activity screening of U. pilulifera against food-borne pathogens. Considering limitations in plant disease control, antibacterial activities of these extracts would be of agricultural importance.

Corchorus olitorius (jute) extract induced cytotoxicity and genotoxicity on human multiple myeloma cells (ARH-77).

CONTEXT: Corchorus olitorius L. (Malvaceae) has industrial importance in world jute production and is a widely cultivated and consumed crop in Cyprus and in some Arabic countries. OBJECTIVE: The present study investigated cytotoxic and genotoxic effects of leaf extracts (LE) and seed extracts (SE) of the C. olitorius on the multiple myeloma-derived ARH-77 cells. The extracts were also evaluated for their total phenol content (TPC) and free radical scavenging activity (FRSA). MATERIALS AND METHODS: C. olitorius was collected from Nicosia, Cyprus. TPC and FRSA were measured by Folin-Ciocalteu and DPPH free radical methods, respectively. Cytotoxicity was evaluated by the MTT assay (4-2048 µg/mL range), and DNA damage (at IC50 and ½IC50) was measured by the comet assay. RESULTS AND DISCUSSION: The LE had significantly higher total phenol (78 mg GAE/g extract) than the SE (2 mg GAE/g extract) with significantly higher FRSA (IC50 LE: 23 µg/mL and IC50 SE: 10 401 µg/mL). Both LE and SE exerted cytotoxic effects on cells after 48 h. The IC50 of SE (17 µg/mL) was lower than LE (151 µg/mL), which demonstrates its higher cytotoxicity on cells. The extracts were applied at 150 and 75 µg/mL for LE and at 17 and 8.5 µg/mL for SE, and the results of the comet assay revealed that the extracts induced genotoxic damage on ARH-77 cells. In both 48 h leaf and seed extract treatments, genotoxic damage significantly increased with increasing concentrations at relevant cytotoxic concentrations. CONCLUSION: To our knowledge, this is the first report demonstrating the high cytotoxic potential of C. olitorius SE and the genotoxic potential of LE and SE.

The impact of developmental genes in non-syndromic cleft lip and/or palate

Non-syndromic cleft lip and/or palate (NSCL/P) is a congenital malformation with a prevalence of 1:700 births. It has a multifactorial etiology. Human craniofacial development takes place during the first 10 weeks of pregnancy. Normal craniofacial development arises from the convergence and fusion of the facial and palatal processes and involves interactions between genes that regulate cell growth, proliferation, differentiation, epithelial-to-mesenchymal transition, and apoptosis. Whole genome/exome analysis, and also genome-wide association studies give us to chance to identify the genetic factors which contribute to the development of NSCL/P. After detecting a cleft lip and/or palate on ultrasonography without associated anomalies, the patient should be evaluated in collaboration with a clinical geneticist, taking into account the many genes and environmental factors involved in NSCL/P etiopathogenesis, and a roadmap for possible genetic diagnosis should be drawn.

Impact of Matrix Metalloproteinases 2 and 9 and Tissue Inhibitor of Metalloproteinase 2 Gene Polymorphisms on Allograft Rejection in Pediatric Renal Transplant Recipients.

OBJECTIVES: Acute and chronic allograft rejection have been continuously an important obstacle in the follow-up of renal transplant recipients. During clinical management, several factors acting simultaneously result in acute rejection and chronic allograft nephropathy. Matrix metalloproteinases and tissue inhibitors of metalloproteinases are responsible for the organization of the extracellular matrix and play roles in cell proliferation and cellular invasion. Changes in matrix metalloproteinase expression levels have been reported to be associated with renal allograft rejection and interstitial fibrosis. In this study, we aimed to investigate functional polymorphisms of MMP2, MMP9, and TIMP2 genes in pediatric renal transplant recipients. MATERIALS AND METHODS: Our study included 68 kidney transplant recipients and 58 control patients. The kidney transplant recipient group was further divided into 2 subgroups: no graft rejection (n = 47) and graft rejection (n =21). MMP2 -735C >T (rs2285053), MMP2 -1306C >T (rs243865), MMP2 -1575G >A (rs243866), MMP9 c.-1562C >T (rs3918242), TIMP2 -418G >C (rs8179090), and TIMP2 303C > T (rs2277698) polymorphisms were analyzed with the use of polymerase chain reaction and restriction fragment-length polymorphism methods. Allele prevalence was compared with reference values of the control group, and Hardy-Weinberg equilibrium was tested. RESULTS: Mean ages were 16.7 ± 3.9 years for the study group and 14.8 ± 5.6 years for the control group. The mean follow-up time after transplant was 37.7 ± 7.9 months. We compared allele frequencies in the 2 groups and calculated a statistically significant difference in rs2285053, rs243865, rs243866, rs3918242, rs8179090, and rs2277698 polymorphism frequencies between the transplant recipients and control patients. When the transplant recipient group was compared in itself with regard to allograft rejection, all investigated polymorphisms except TIMP2 -418G >C (rs8179090) revealed a statistically significant difference between those with and without rejection (P < .05). CONCLUSIONS: Matrix metalloproteinases and their tissue inhibitors could be important predictive biological markers for the follow-up of kidney transplant recipients.

Fetal axillary cystic hygroma: a novel association with triple X syndrome.

BACKGROUND: Triple X syndrome is a relatively common sex chromosomal aneuploidy with an estimated incidence of one in every 1000 female births. There is considerable diversity in phenotypes among patients with triple X syndrome. Triple X syndrome has been shown to have associated abnormalities, with genitourinary malformations being the most consistent. Cystic hygroma (CH) is a lymphatic malformation that occurs because of the lack of development of communication between the lymphatic and the venous systems. CH has an incidence of 1 in every 6000-10,000 live births. CH is associated with a variety of conditions, including chromosomal aneuploidies and fetal malformations. CASE: We report a case of prenatally detected triple X syndrome with axillary CH as an isolated finding. The patient was referred because of a fetal cystic mass at the right axillary region. Amniocentesis revealed 47,XXX karyotype, and no additional abnormalities were detected prenatally or after abortion. CONCLUSION: This is a novel description of axillary CH associated with triple X syndrome.

Transient hydrops fetalis in a prenatally diagnosed pentasomy X?

Numerical abnormalities of sex chromosomes are seen approximately 1 in 400 live births. Pentasomy X is a very rare chromosomal abnormality and it is defined as presence of five X chromosomes instead of two. Prenatal sonographic features have rarely been described in the literature before. Here we present a non-immune fetal hydrops diagnosed during the 17th week of gestation. Ultrasonographic examination revealed subcutaneous edema, pleural effusion and ascites, and also clinodactyly of the fifth fingers of both hands. The fetal karyotype was assessed as 49,XXXXX (pentasomy X) in two different culture flasks. Hydropic signs regressed at 21 weeks' gestation. Prenatal diagnosis may not be possible usually for this rare chromosomal abnormality. Every anomaly detected prenatally, such as transient hydrops, may help us to diagnose pentasomy X.

Effects of ascorbic acid and ß-carotene on HepG2 human hepatocellular carcinoma cell line.

Recent studies have demonstrated that vegetable rich diets have protective effects on the occurrence and prognosis of various cancers. In addition to dietary intakes, ascorbic acid and ß-carotene are also taken as supplements. The aim of this study was to assess effects of ascorbic acid, ß-carotene and their combinations on human hepatocellular carcinoma cell line HepG2. Ascorbic acid and ß-carotene were applied to cells as plasma peak concentrations (70 and 8 µM, respectively) and their half concentrations (35 and 4 µM, respectively) for 24 and 48 h. Genotoxic and cytotoxic effects of ascorbic acid and ß-carotene were evaluated by alkali single cell gel electrophoresis (SCGE), acridine orange/ethidium bromide staining patterns of cells (apoptosis and necrosis) and lipid peroxidation (thiobarbituric acid reactive substances, TBARS). Results of the SCGE demonstrated that both ascorbic acid and ß-carotene caused DNA damage on HepG2 which were also concordant to increased apoptosis and necrosis of cells. Increased TBARS values also demonstrated increased lipid peroxidation in these cells. Results of the present study demonstrates that when dietary intakes of ascorbic acid and ß-carotene and their relevant achievable plasma level concentrations were considered, both ascorbic acid and ß-carotene induce genotoxic and cytotoxic damage on HepG2 together with increased oxidative damage in contrast to their protective effect on healthy cells. This may be correlated to oxidative status and balance of ROS in hepatocellular carcinoma cells.

Copper-induced oxidative damage, antioxidant response and genotoxicity in Lycopersicum esculentum Mill. and Cucumis sativus L.

Adequate copper (Cu(2+)) concentrations are required for plants; however, at higher concentrations it can also cause multiple toxic effects. In the present study, lipid peroxidation, hydrogen peroxide levels as well as ascorbate peroxidase (APX: EC 1/11/1/11) and catalase (CAT: EC 1.11.1.6) activities were determined in Lycopersicum esculentum Mill. and Cucumis sativus L. seedlings after 7-day exposure to copper sulfate. In addition, DNA damage in these two crops was assessed by measuring micronucleus (MN) frequency and tail moments (TM) as determined by Comet assay. Inhibitory copper concentrations (EC(50): 30 and 5.5 ppm for L. esculentum and C. sativus, respectively) were determined according to dose-dependent root inhibition curves, and EC(50) and 2×EC(50) were applied. Malondialdehyde (MDA) and H(2)O(2) levels significantly increased in all groups studied. CAT activity increased in treatment groups of C. sativus. APX activity increased in L. esculentum seedlings due to 2×EC(50) treatment. Reductions in mitotic indices (MI) represented Cu(2+)dependent root growth inhibition in all treatment groups studied. According to TMs and MN frequencies, copper exposure induced significant DNA damage (p < 0.05) in all study groups, whereas the DNA damage induced was dose dependent in C. sativus roots. In conclusion, Cu(2+)induced oxidative damage, elevations in H(2)O(2) levels and alterations in APX and CAT activities, as well as significant DNA damage in nuclei of both study groups. To our knowledge, this is the first comparative and comprehensive study demonstrating the effects of copper on two different plant species at relevant cytotoxic concentrations at both biochemical and genotoxicity levels with multiple end points.

Fluorescence in situ hybridization analysis of the hTERC region in acute myeloid leukemia patients.

OBJECTIVE: The telomerase RNA component (hTERC) gene is located at 3q26. Increased hTERC gene expression has been frequently observed and amplification was shown using fluorescence in situ hybridization (FISH) in different cancers. The aim of this study was to determine whether hTERC gene amplification is detectable by FISH in acute myeloid leukemia (AML) cells. METHODS: FISH and karyotype results at the time of diagnosis of 23 adult AML patients were retrospectively evaluated. Additionally, fixed cells were hybridized with an hTERC region-specific FISH probe to determine gene amplification. RESULTS: Ten of the 23 patients had a normal karyotype and 6 had an abnormal karyotype. hTERC region amplification was not observed in any of the patients. CONCLUSION: Although it was reported that hTERC gene amplification may partially contribute to increased telomerase expression and activity in leukemic cells, it is not possible to make such a conclusion based on the results of the this study, as hTERC amplification was not observed in the study group. This suggests that increased telomerase activity via gene amplification in the development of AML may not be as important a factor as it is in solid tumors.

Complex cytogenetic findings in the bone marrow of a chronic idiopathic myelofibrosis patient.

Chronic idiopathic myelofibrosis is a myeloproliferative disorder characterized by splenomegaly, myeloid metaplasia and reactive bone marrow fibrosis. Karyotype analysis of the bone marrow is an integral part of the diagnosis, especially as a discriminative tool in ruling out reactive conditions. The frequency of clonal cytogenetic anomalies in this disease is the highest among its group, varying between 30 and 75%. Among these, trisomy 1q, 20q-, 13q- and +8 are the most common aberrations. Here we report a 66-year-old male patient whose bone marrow biopsy revealed signs of chronic myeloproliferative changes and dysmegakaryopoiesis. He was administered hydroxyurea treatment, splenic radiotherapy and multiple transfusions. The patient worsened in the following months and the second bone marrow biopsy revealed myelofibrosis. Cytogenetic analysis of this bone marrow sample revealed a complex karyotype reported to be 46,XY,del(9)(q22q34),t(8;17;21)(q22;q21;q22)[23]/46,XY[2], with a previously undefined three-way translocation and deletion in chromosome 9. The patient died shortly thereafter.