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Background: Tooth agenesis refers to the absence of one or more of the deciduous or permanent teeth. Tooth agenesis results from a series of disrupted reciprocal ectodermal mesenchymal interactions taking place during the early stages of tooth development. Methods: A narrative literature review was performed to describe the main genetic syndromes associated with tooth agenesis. Results and conclusions: The etiology of congenital tooth agenesis is multifactorial and include genetic, epigenetic, and environmental influences. Syndromes associated with chromosomal alterations, ectodermal dysplasia, Axenfeld-Rieger syndrome, oral-facial cleft syndromes, and syndromes with cancer predisposition are among the main entities presenting with tooth agenesis. Clinical relevance: Tooth agenesis disorders can affect the masticatory function and cause disfigurement leading to physiological and psychological complications. Early recognition of these entities is crucial to guide the management of the patient and to provide families with the appropriate genetic counseling. [ABSTRACT FROM AUTHOR]

Summary: Severe aplastic anaemia (SAA) is a rare and life‐threatening bone marrow failure disorder. We used data from the transplant outcomes in aplastic anaemia study to characterize mosaic chromosomal alterations (mCAs) in the peripheral blood of 738 patients with acquired SAA and evaluate their associations with telomere length (TL) and survival post‐haematopoietic cell transplant (HCT). The median age at HCT was 20.4 years (range = 0.2–77.4). Patients with SAA had shorter TL than expected for their age (median TL percentile for age: 35.7th; range <1–99.99). mCAs were detected in 211 patients (28.6%), with chr6p copy‐neutral loss of heterozygosity (6p‐CNLOH) in 15.9% and chr7 loss in 3.0% of the patients; chrX loss was detected in 4.1% of female patients. Negative correlations between mCA cell fraction and measured TL (r = −0.14, p = 0.0002), and possibly genetically predicted TL (r = −0.07, p = 0.06) were noted. The post‐HCT 3‐year survival probability was low in patients with chr7 loss (39% vs. 72% in patients with chr6‐CNLOH, 60% in patients with other mCAs and 70% in patients with no mCAs; p‐log rank = 0.001). In multivariable analysis, short TL (p = 0.01), but not chr7 loss (p = 0.29), was associated with worse post‐HCT survival. TL may guide clinical decisions in patients with SAA. [ABSTRACT FROM AUTHOR]

Purpose: Coal mining is a vital sector in Colombia, contributing significantly to the nation's economy and the development of its regions. However, despite its importance, it has led to a gradual decline in the health of mine workers and nearby residents. While the adverse health effects of open-pit coal mining on exposed individuals have been well-documented in Colombia and globally, studies investigating genetic damage in underground coal miners are lacking. Methods: The aim of our study was to evaluate chromosomal and genotoxic damage, in peripheral blood samples from a group of underground coal miners and residents of areas exposed to coal, in the town of Samacá, Boyacá-Colombia, and in a group of unexposed individuals by using banding and molecular cytogenetic techniques, as well as cytokinesis block micronucleus assays. Results: Our results suggest that occupational exposure to coal induces chromosomal and genotoxic damage in somatic cells of underground coal miners. Chromosomal and genotoxic damage is an important step in carcinogenesis and the development of many other diseases. Our findings provide valuable insights into the effects of coal dust exposure on chromosomal integrity and genetic stability. Conclusion: Our pilot study suggests that occupational exposure to coal induces chromosomal damage in underground coal miners, highlighting the importance of validating these findings with a larger sample size. Our results highlight the need to implement prevention and protection measures, as well as educational programs for underground coal miners. Characterizing and estimating exposure risks are extremely important for the safety of people exposed occupationally and environmentally to coal and its derivatives. [ABSTRACT FROM AUTHOR]

Plant breeding, aimed at enhancing desired traits, depends on genetic diversity. Mutation breeding is a powerful method of rapidly expanding genetic diversity, facilitating crop improvement, and ensuring food security. In a recent study, researchers evaluated the genetic variability of Trigonella species using different doses of sodium azide (SA) (0.2%, 0.4%, 0.6%, 0.8%, and 1.0%) through morphological, physiological, and cytogenetic studies. Morphological variations were observed in cotyledonary leaves, vegetative leaves, and overall plant growth and habit. Several quantitative parameters, such as plant height, fertile branches per plant, pods per plant (or clusters), seeds per pod, and seed yield, increased when treated with 0.2% and 0.4% SA compared to the control. Furthermore, the total chlorophyll content and carotenoids increased in the sample treated with 0.2% SA over the control but decreased with higher concentrations. Scanning electron microscopy revealed that stomatal aperture and seed dimensions increased at lower concentrations of sodium azide treatment. The study found a positive correlation between the different parameters studied in the Trigonella species, as indicated by high r-values. Based on their findings, it was concluded that the genotype of fenugreek can be improved by using 0.2% and 0.4% concentrations of sodium azide. However, the evaluation of observed variants in successive generations is a critical and necessary process to validate their potential as keystones for crop genetic improvements. [ABSTRACT FROM AUTHOR]

PurposeCoal mining is a vital sector in Colombia, contributing significantly to the nation’s economy and the development of its regions. However, despite its importance, it has led to a gradual decline in the health of mine workers and nearby residents. While the adverse health effects of open-pit coal mining on exposed individuals have been well-documented in Colombia and globally, studies investigating genetic damage in underground coal miners are lacking.MethodsThe aim of our study was to evaluate chromosomal and genotoxic damage, in peripheral blood samples from a group of underground coal miners and residents of areas exposed to coal, in the town of Samacá, Boyacá-Colombia, and in a group of unexposed individuals by using banding and molecular cytogenetic techniques, as well as cytokinesis block micronucleus assays.ResultsOur results suggest that occupational exposure to coal induces chromosomal and genotoxic damage in somatic cells of underground coal miners. Chromosomal and genotoxic damage is an important step in carcinogenesis and the development of many other diseases. Our findings provide valuable insights into the effects of coal dust exposure on chromosomal integrity and genetic stability.ConclusionOur pilot study suggests that occupational exposure to coal induces chromosomal damage in underground coal miners, highlighting the importance of validating these findings with a larger sample size. Our results highlight the need to implement prevention and protection measures, as well as educational programs for underground coal miners. Characterizing and estimating exposure risks are extremely important for the safety of people exposed occupationally and environmentally to coal and its derivatives.

Plant breeding, aimed at enhancing desired traits, depends on genetic diversity. Mutation breeding is a powerful method of rapidly expanding genetic diversity, facilitating crop improvement, and ensuring food security. In a recent study, researchers evaluated the genetic variability of Trigonella species using different doses of sodium azide (SA) (0.2%, 0.4%, 0.6%, 0.8%, and 1.0%) through morphological, physiological, and cytogenetic studies. Morphological variations were observed in cotyledonary leaves, vegetative leaves, and overall plant growth and habit. Several quantitative parameters, such as plant height, fertile branches per plant, pods per plant (or clusters), seeds per pod, and seed yield, increased when treated with 0.2% and 0.4% SA compared to the control. Furthermore, the total chlorophyll content and carotenoids increased in the sample treated with 0.2% SA over the control but decreased with higher concentrations. Scanning electron microscopy revealed that stomatal aperture and seed dimensions increased at lower concentrations of sodium azide treatment. The study found a positive correlation between the different parameters studied in the Trigonella species, as indicated by high r-values. Based on their findings, it was concluded that the genotype of fenugreek can be improved by using 0.2% and 0.4% concentrations of sodium azide. However, the evaluation of observed variants in successive generations is a critical and necessary process to validate their potential as keystones for crop genetic improvements.

Heliotropium elongatum is used to treat inflammation, cough, and flu. This study aimed to characterize the phytochemical profile and determine the total phenolic content (TPC), antioxidant and cytogenotoxic activity of the ethanolic extract (EE), and fractions of H. elongatum leaves. In the phytochemical profile analysis, organic acids, reducing sugars, flavonoids, saponins, anthraquinones, steroids/triterpenes, and depsides/depsidones were detected in the EE and/or fractions (hexanic/FH, chloroformic/FC, ethyl acetate/FAE, and hydromethanolic/FHM). The highest TPC and highest antioxidant activity (DPPH and ABTS) was detected in FHM. In FH, 16 compounds were identified by GC-MS, and ursolic acid was isolated by 1H NMR and 13C NMR. HPLC-DAD from EE, FAE, and FHM demonstrated characteristic wavelengths for flavonoids, flavonols, flavones, and anthraquinones. ESI-IT/MSn analysis of EE, FC, FAE, and FHM revealed alkaloids, steroids, terpenoids, flavonoids, and phenolic acids. In Allium cepa assay there was no significant cytotoxic effect initiated by EE (62.5 to 1,000 µg/ml), FHM (1,000 µg/ml), and FAE (62.5 µg/ml). Genotoxicity was evidenced only with EE at 500 and 1,000 µg/ml, and FHM (62.5 to 1,000 µg/ml) as evidenced by presence of micronuclei (MN) and nuclear buds (NB). Our results identified compounds of medicinal interest with antioxidant activity; however observed cytogenotoxic changes indicated the need for caution when using these compounds for therapeutic purposes. [ABSTRACT FROM AUTHOR]

Genetic variation is a well-known contributor to the onset and progression of cancer. The goal of this study is to provide a comprehensive examination of the nucleotide and chromosomal variation associated with the onset and progression of serous ovarian cancer. Using a variety of computational and statistical methods, we examine the exome sequence profiles of genetic variants present in the primary tumors of 432 ovarian cancer patient samples to compute: (1) the tumor mutational burden for all genes and (2) the chromosomal copy number alterations associated with the onset/progression of ovarian cancer. Tumor mutational burden is reduced in the late vs. early stages, with the highest levels being associated with loss-of-function mutations in DNA-repair genes. Nucleotide variation and copy number alterations associated with known cancer driver genes are selectively favored over ovarian cancer development. The results indicate that genetic variation is a significant contributor to the onset and progression of ovarian cancer. The measurement of the relative levels of genetic variation associated with individual ovarian cancer patient tumors may be a clinically valuable predictor of potential tumor aggressiveness and resistance to chemotherapy. Tumors found to be associated with high levels of genetic variation may help in the clinical identification of high-risk ovarian cancer patients who could benefit from more frequent monitoring. [ABSTRACT FROM AUTHOR]

The use of eco-friendly engineered nanomaterials represents a recent solution for an effective and safe treatment of contaminated dredging sludge. In this study, an eco-designed engineered material based on cross-linked nanocellulose (CNS) was applied for the first time to decontaminate a real matrix from heavy metals (namely Zn, Ni, Cu, and Fe) and other undesired elements (mainly Ba and As) in a lab-scale study, with the aim to design a safe solution for the remediation of contaminated matrices. Contaminated freshwater sludge was treated with CNS coupled with a filtering fine-mesh net, and the obtained waters were tested for acute and sublethal toxicity. In order to check the safety of the proposed treatment system, toxicity tests were conducted by exposing the bacterium Aliivibrio fischeri and the crustacean Heterocypris incongruens, while subtoxicity biomarkers such as lysosomal membrane stability, genetic, and chromosomal damage assessment were performed on the freshwater bivalve Dreissena polymorpha. Dredging sludge was found to be genotoxic, and such genotoxicity was mitigated by the combined use of CNS and a filtering fine-mesh net. Chemical analyses confirmed the results by highlighting the abetment of target contaminants, indicating the present model as a promising tool in freshwater sludge nanoremediation. [ABSTRACT FROM AUTHOR]

Purpose: Structural mosaicism has been previously implicated in developmental disorders. We aimed to identify rare mosaic chromosomal alterations (MCAs) in probands with severe undiagnosed developmental disorders. Methods: We identified MCAs in genotyping array data from 12,530 probands in the Deciphering Developmental Disorders study using mosaic chromosome alterations caller (MoChA). Results: We found 61 MCAs in 57 probands, many of these were tissue specific. In 23 of 26 (88.5%) cases for which the MCA was detected in saliva in which blood was also available for analysis, the MCA could not be detected in blood. The MCAs included 20 polysomies, comprising either 1 arm of a chromosome or a whole chromosome, for which we were able to show the timing of the error (25% mitosis, 40% meiosis I, and 35% meiosis II). Only 2 of 57 (3.5%) of the probands in whom we found MCAs had another likely genetic diagnosis identified by exome sequencing, despite an overall diagnostic yield of ∼40% across the cohort. Conclusion: Our results show that identification of MCAs provides candidate diagnoses for previously undiagnosed patients with developmental disorders, potentially explaining ∼0.45% of cases in the Deciphering Developmental Disorders study. Nearly 90% of these MCAs would have remained undetected by analyzing DNA from blood and no other tissue.

Simple Summary: Chromosomal alterations and other structural variants have been recurrently identified in Wilms tumors (WT) and are promising biomarkers for risk stratification. Chromosome 1q gain occurs in one in three WTs and is associated with poor prognosis, but its impact on tumor biology remains unknown. Here, we investigated the mutational mechanisms and functional effects of chromosomal alterations in WTs, and in particular 1q gain. We identified subgroups of tumors with typical activated biological processes: muscle differentiation, immune system, kidney development and proliferation. Combining these subgroups with genomic data showed that tumors with 1q gain occur in all subgroups and can be associated with different functional effects. Also, 1q gain tumors differ in mutational mechanisms and co-occurring tumor-specific mutations. In conclusion, we identified subgroups of tumors with 1q gain and therefore propose that incorporating expression data in risk stratification could improve the clinical utility of 1q gain. Chromosomal alterations have recurrently been identified in Wilms tumors (WTs) and some are associated with poor prognosis. Gain of 1q (1q+) is of special interest given its high prevalence and is currently actively studied for its prognostic value. However, the underlying mutational mechanisms and functional effects remain unknown. In a national unbiased cohort of 30 primary WTs, we integrated somatic SNVs, CNs and SVs with expression data and distinguished four clusters characterized by affected biological processes: muscle differentiation, immune system, kidney development and proliferation. Combined genome-wide CN and SV profiles showed that tumors profoundly differ in both their types of 1q+ and genomic stability and can be grouped into WTs with co-occurring 1p−/1q+, multiple chromosomal gains or CN neutral tumors. We identified 1q+ in eight tumors that differ in mutational mechanisms, subsequent rearrangements and genomic contexts. Moreover, 1q+ tumors were present in all four expression clusters reflecting activation of various biological processes, and individual tumors overexpress different genes on 1q. In conclusion, by integrating CNs, SVs and gene expression, we identified subgroups of 1q+ tumors reflecting differences in the functional effect of 1q gain, indicating that expression data is likely needed for further risk stratification of 1q+ WTs. [ABSTRACT FROM AUTHOR]

Sugarcane straw burning generates particulate matter with complex composition resulting in atmosphere pollution. Sugarcane straw sugarcane burning particles (PSSB) contain several chemical compounds that were previously identified to be associated with carcinogenic and mutagenic processes. The aim of the present study was to extract PSSB under lab conditions and subsequently determine phyto- and cytogenotoxicity of these particles using Lactuca sativa L. and Allium cepa L. bioassays. Seeds of lettuce var. Cinderela and onion cv. Vale-Ouro IPA-11 were germinated in Petri dishes containing different concentrations of PSSB at 25, 50, 100, 200 or 300 mg/ml as well as control for 72 hr. Seed germination of lettuce was inhibited by PSSB, in a concentration-dependent manner, accompanied by decreased root growth, suggesting phytotoxic effects. Further, reduction of mitotic index and high number of chromosomal alterations in onion of meristematics cells indicated a cytogenotoxic action attributed to PSSB. Although the chemical composition of PSSB in question has not been determined, the phyto- and cytogenotoxic effects may be linked to the possible presence of polycyclic aromatic hydrocarbons (PAHs), which are were identified as the main constituents of particulate matter resulting from burning of sugarcane straw, in addition to exerting adverse biological effects that might result in mutations and cancer. Data demonstrated that the use of plants bioassays might be an important tool for biomonitoring air quality. [ABSTRACT FROM AUTHOR]

Pesticides are a group of environmental pollutants widely used in agriculture to protect crops, and their indiscriminate use has led to a growing public awareness about the health hazards associated with exposure to these substances. In fact, exposure to pesticides has been associated with an increased risk of developing diseases, including cancer. In a study previously published by us, we observed the induction of specific chromosomal alterations and, in general, the deleterious effect of pesticides on the chromosomes of five individuals exposed to pesticides. Considering the importance of our previous findings and their implications in the identification of cytogenetic biomarkers for the monitoring of exposed populations, we decided to conduct a new study with a greater number of individuals exposed to pesticides. Considering the above, the aim of this study was to evaluate the type and frequency of chromosomal alterations, chromosomal variants, the level of chromosomal instability and the clonal heterogeneity in a group of thirty-four farmers occupationally exposed to pesticides in the town of Simijacá, Colombia, and in a control group of thirty-four unexposed individuals, by using Banding Cytogenetics and Molecular Cytogenetics (Fluorescence in situ hybridization). Our results showed that farmers exposed to pesticides had significantly increased frequencies of chromosomal alterations, chromosomal variants, chromosomal instability and clonal heterogeneity when compared with controls. Our results confirm the results previously reported by us, and indicate that occupational exposure to pesticides induces not only chromosomal instability but also clonal heterogeneity in the somatic cells of people exposed to pesticides. This study constitutes, to our knowledge, the first study that reports clonal heterogeneity associated with occupational exposure to pesticides. Chromosomal instability and clonal heterogeneity, in addition to reflecting the instability of the system, could predispose cells to acquire additional instability and, therefore, to an increased risk of developing diseases. [ABSTRACT FROM AUTHOR]

Soybean represents a valuable source of food for humans and animals and the quality of the seeds has great importance for the establishment and high productivity of this crop. Soybean seeds require continuous improvement, which is dependent on a better understanding of the regulatory mechanisms that coordinate seed germination. To investigate whether the method of water absorption into soybean seeds could lead to abnormal seedlings, and if this could be associated with cytogenetical consequences, we premoistened the seeds of three cultivars; M 6410 IPRO, M6210 IPRO, and BMX Potência RR by direct immersion (fast method), use of a wet substrate (intermediate method), and by moist atmosphere (slow method) with distilled water at 25ºC for 24 hours. We investigated the normal and abnormal seedlings, electrical conductivity, mitosis, cell death, and the chromosomal abnormalities index. The comet assay was applied to investigate DNA fragmentation. Direct immersion in water induced seedling growth inhibition and caused cytological alterations associated with genotoxicity effects in the studied soybean genotypes. Slow premoistening of the seeds increased seedling performance as a result of higher final germination percentage (above 85%), reduced abnormal seedlings (below 5%, on average), and reduced the electrical conductivity of seeds. All three genotypes of soybean seeds lost their ability to withstand the imbibitional damage induced by direct immersion as abnormal seedlings increased. We concluded that the fast water absorption by seeds poses a threat to genomic integrity owing to its potential for genotoxicity to DNA, manifesting as breaks or loss of whole chromosomes. Slow premoistening of the seeds resulted in a longer time period to deal with damage. Stabilized seedling growth was provided by altering cytogenetic responses during uptake of water by soybean seeds through the maintenance of cell viability.

Pesticides are a group of environmental pollutants widely used in agriculture to protect crops, and their indiscriminate use has led to a growing public awareness about the health hazards associated with exposure to these substances. In fact, exposure to pesticides has been associated with an increased risk of developing diseases, including cancer. In a study previously published by us, we observed the induction of specific chromosomal alterations and, in general, the deleterious effect of pesticides on the chromosomes of five individuals exposed to pesticides. Considering the importance of our previous findings and their implications in the identification of cytogenetic biomarkers for the monitoring of exposed populations, we decided to conduct a new study with a greater number of individuals exposed to pesticides. Considering the above, the aim of this study was to evaluate the type and frequency of chromosomal alterations, chromosomal variants, the level of chromosomal instability and the clonal heterogeneity in a group of thirty-four farmers occupationally exposed to pesticides in the town of Simijacá, Colombia, and in a control group of thirty-four unexposed individuals, by using Banding Cytogenetics and Molecular Cytogenetics (Fluorescence in situ hybridization). Our results showed that farmers exposed to pesticides had significantly increased frequencies of chromosomal alterations, chromosomal variants, chromosomal instability and clonal heterogeneity when compared with controls. Our results confirm the results previously reported by us, and indicate that occupational exposure to pesticides induces not only chromosomal instability but also clonal heterogeneity in the somatic cells of people exposed to pesticides. This study constitutes, to our knowledge, the first study that reports clonal heterogeneity associated with occupational exposure to pesticides. Chromosomal instability and clonal heterogeneity, in addition to reflecting the instability of the system, could predispose cells to acquire additional instability and, therefore, to an increased risk of developing diseases.

Soybean represents a valuable source of food for humans and animals and the quality of the seeds has great importance for the establishment and high productivity of this crop. Soybean seeds require continuous improvement, which is dependent on a better understanding of the regulatory mechanisms that coordinate seed germination. To investigate whether the method of water absorption into soybean seeds could lead to abnormal seedlings, and if this could be associated with cytogenetical consequences, we premoistened the seeds of three cultivars; M 6410 IPRO, M6210 IPRO, and BMX Potência RR by direct immersion (fast method), use of a wet substrate (intermediate method), and by moist atmosphere (slow method) with distilled water at 25°C for 24 hours. We investigated the normal and abnormal seedlings, electrical conductivity, mitosis, cell death, and the chromosomal abnormalities index. The comet assay was applied to investigate DNA fragmentation. Direct immersion in water induced seedling growth inhibition and caused cytological alterations associated with genotoxicity effects in the studied soybean genotypes. Slow premoistening of the seeds increased seedling performance as a result of higher final germination percentage (above 85%), reduced abnormal seedlings (below 5%, on average), and reduced the electrical conductivity of seeds. All three genotypes of soybean seeds lost their ability to withstand the imbibitional damage induced by direct immersion as abnormal seedlings increased. We concluded that the fast water absorption by seeds poses a threat to genomic integrity owing to its potential for genotoxicity to DNA, manifesting as breaks or loss of whole chromosomes. Slow premoistening of the seeds resulted in a longer time period to deal with damage. Stabilized seedling growth was provided by altering cytogenetic responses during uptake of water by soybean seeds through the maintenance of cell viability. [ABSTRACT FROM AUTHOR]

The use of eco-friendly engineered nanomaterials represents a recent solution for an effective and safe treatment of contaminated dredging sludge. In this study, an eco-designed engineered material based on cross-linked nanocellulose (CNS) was applied for the first time to decontaminate a real matrix from heavy metals (namely Zn, Ni, Cu, and Fe) and other undesired elements (mainly Ba and As) in a lab-scale study, with the aim to design a safe solution for the remediation of contaminated matrices. Contaminated freshwater sludge was treated with CNS coupled with a filtering fine-mesh net, and the obtained waters were tested for acute and sublethal toxicity. In order to check the safety of the proposed treatment system, toxicity tests were conducted by exposing the bacterium Aliivibrio fischeri and the crustacean Heterocypris incongruens, while subtoxicity biomarkers such as lysosomal membrane stability, genetic, and chromosomal damage assessment were performed on the freshwater bivalve Dreissena polymorpha. Dredging sludge was found to be genotoxic, and such genotoxicity was mitigated by the combined use of CNS and a filtering fine-mesh net. Chemical analyses confirmed the results by highlighting the abetment of target contaminants, indicating the present model as a promising tool in freshwater sludge nanoremediation.

Abstract Piperine and capsaicin are important molecules with biological and pharmacological activities. This study aimed to evaluate the cytogenotoxic and protective effect of piperine and capsaicin on Allium cepa cells. A. cepa roots were exposed to negative (2% Dimethylsulfoxide) and positive (Methylmethanesulfonate, MMS, 10 µg/mL) controls, and four concentrations (25-200 µM) of piperine or capsaicin (alone) or associated before, simultaneously or after with the MMS. Only the lowest concentration of piperine (25 µM) showed a protective effect because it was not genotoxic. Piperine and capsaicin were cytotoxic (50, 100 and 200 µM). Piperine (50 to 200 µM) caused a significant increase in the total average of chromosomal alterations of in A. cepa cells. For capsaicin, the genotoxic effect was dose-dependent with a significant increase for all concentrations, highlighting the significant presence of micronuclei and nuclear buds for the two isolates. In general, bioactive compounds reduced the total average of chromosomal alterations against damage caused by MMS, mainly micronuclei and/or nuclear buds. Therefore, the two molecules were cytotoxic and genotoxic at the highest concentrations, and did not have cytoprotective action, and the lowest concentration of piperine demonstrated important chemopreventive activity.

Abstract Background Interspecific hybridisation resulting in polyploidy is one of the major driving forces in plant evolution. Here, we present data from the molecular cytogenetic analysis of three cytotypes of Elytrigia ×mucronata using sequential fluorescence (5S rDNA, 18S rDNA and pSc119.2 probes) and genomic in situ hybridisation (four genomic probes of diploid taxa, i.e., Aegilops, Dasypyrum, Hordeum and Pseudoroegneria). Results The concurrent presence of Hordeum (descended from E. repens) and Dasypyrum + Aegilops (descended from E. intermedia) chromosome sets in all cytotypes of E. ×mucronata confirmed the assumed hybrid origin of the analysed plants. The following different genomic constitutions were observed for E. ×mucronata. Hexaploid plants exhibited three chromosome sets from Pseudoroegneria and one chromosome set each from Aegilops, Hordeum and Dasypyrum. Heptaploid plants harboured the six chromosome sets of the hexaploid plants and an additional Pseudoroegneria chromosome set. Nonaploid cytotypes differed in their genomic constitutions, reflecting different origins through the fusion of reduced and unreduced gametes. The hybridisation patterns of repetitive sequences (5S rDNA, 18S rDNA, and pSc119.2) in E. ×mucronata varied between and within cytotypes. Chromosome alterations that were not identified in the parental species were found in both heptaploid and some nonaploid plants. Conclusions The results confirmed that both homoploid hybridisation and heteroploid hybridisation that lead to the coexistence of four different haplomes within single hybrid genomes occur in Elytrigia allopolyploids. The chromosomal alterations observed in both heptaploid and some nonaploid plants indicated that genome restructuring occurs during and/or after the hybrids arose. Moreover, a specific chromosomal translocation detected in one of the nonaploids indicated that it was not a primary hybrid. Therefore, at least some of the hybrids are fertile. Hybridisation in Triticeae allopolyploids clearly and significantly contributes to genomic diversity. Different combinations of parental haplomes coupled with chromosomal alterations may result in the establishment of unique lineages, thus providing raw material for selection.

Breast implant–associated anaplastic large cell lymphoma (BIA-ALCL) is an uncommon form of non-Hodgkin lymphoma (cancer of the immune system) that can develop around breast implants. Breast implants are among the most commonly used medical devices for cosmetic or reconstructive purposes. In the past few years, the number of women with breast implants diagnosed with anaplastic large cell lymphoma (ALCL) has increased, and several studies have suggested a direct association between breast implants and an increased risk of this disease. Although it has been hypothesized that chronic stimulation of the immune system caused by implant materials and biofilms as well as a possible genetic predisposition play an important role in this disease, the cellular and molecular causes of BIA-ALCL are not fully understood. This review aims to describe the current understanding around the environmental and molecular drivers of BIA-ALCL as well as the genetic and chromosomal abnormalities identified in this disease to date. [ABSTRACT FROM AUTHOR]

Coal and its byproducts and mineral waste constitute complex mixtures, which contain a variety of chemical compounds that impact the ecosystems. For this reason, procedures are required to monitor coal-degraded areas, including the use of biomonitoring organisms. In this light, the aim of the present study was to evaluate the cytotoxicity, genotoxicity, mutagenicity, and phytotoxicity of the aerial part and root extracts from Eragrostis plana Nees collected in the surroundings of the Thermoelectric Power Plant President Médici-UTPM (Candiota, Brazil), through Allium cepa bioassay. Cytotoxicity, genotoxicity, and mutagenicity in the A. cepa meristematic cells were verified through the mitotic index (MI), chromosomal alterations, and micronucleus formation, respectively. In addition, the germination rate, vigor index, and morphological abnormalities were verified in A. cepa seedlings. Treatment with root extracts from E. plana (ACR) specimens collected in a coal-contaminated region resulted in the lowest MI values (8.9%, 12.7%, and 16.0%), representing the most cytotoxic effect when compared with the negative control—NC (dH2O) (MI = 35.8%). ACR extract also was the most genotoxic and mutagenic sample compared with NC and other treatments. Phytotoxicity analyses corroborated the toxic action of ACR, presenting abnormal seedlings and change in vigor index. The high concentration of dissolved total chlorides and electrical conductivity presented in the root extracts of E. plana, which were grown in the carboniferous region, indicates an increase in the absorption of metallic ions and organic compound and supports the hypothesis that this species has bioaccumulator potential, being a new biomonitor model of coal-contaminated region. [ABSTRACT FROM AUTHOR]

Background: Primary amenorrhea (PA) is proposed to have multiple etiological factors that include genetic factors, intrauterine malformations, endocrine dysfunction and environmental factors, as revealed by previous studies pertaining to amenorrhea. However, among the various proposed etiologies, genetic factors appear to be highly associated with PA as approximately 40% of PA cases have been found to have genetic causes. Aim of the study: The present study was proposed to establish the frequency and pattern of chromosomal abnormalities in PA cases of Kashmir. Subjects and methods: A total of 108 females within the age group of 14–33 years and having a history of amenorrhea were included in the study. Peripheral blood lymphocyte cultures were set for each subject according to standard protocol and chromosomal analysis was carried out on well spread metaphases by the help of Cytovision software Version 3.9. Results: The results of the present study reveal that the incidence of chromosomal abnormalities in PA cases of this region is almost similar with those of many reports around the world. However, we report two unique chromosomal alterations viz., 46,XX, dup2q(13) and 46,XX, t(2,5)(p11.2;q34) that have not been found elsewhere in the literature. Conclusion: The results of the present study indicate that chromosomal analysis of females with PA, after the exclusion of non-genetic causes, should be essentially considered for the precise diagnosis and the development of more successful treatment. The study being the first of its kind in this part of the world forms the basis for further studies of the PA cases of this region. The precise molecular characterization of the unique breakpoint regions reported in our study can possibly help in the identification of new genes involved in primary amenorrhea.

Skin toad secretion present physiologically active molecules to protect them against microorganisms, predators and infections. This work detailed the antiproliferative action of marinobufagin on tumor and normal lines, investigate its mechanism on HL-60 leukemia cells and its toxic effects on Allium cepa meristematic cells. Initially, cytotoxic action was assessed by colorimetric assays. Next, HL-60 cells were analyzed by morphological and flow cytometry techniques and growing A. cepa roots were examined after 72 h exposure. Marinobufagin presented high antiproliferative action against all human tumor lines [IC 50 values ranging from 0.15 (leukemia) to 7.35 (larynx) μM] and it failed against human erythrocytes and murine lines. Human normal peripheral blood mononuclear cells (PBMC) were up to 72.5-fold less sensitive [IC 50: 10.88 μM] to marinobufagin than HL-60 line, but DNA strand breaks were no detected. Leukemia treaded cells exhibited cell viability reduction, DNA fragmentation, phosphatidylserine externalization, binucleation, nuclear condensation and cytoplasmic vacuoles. Marinobufagin also reduced the growth of A. cepa roots (EC 50 : 7.5 μM) and mitotic index, caused cell cycle arrest and chromosomal alterations (micronuclei, delays and C-metaphases) in meristematic cells. So, to find out partially targeted natural molecules on human leukemia cells, like marinobufagin, is an amazing and stimulating way to continue the battle against cancer. [ABSTRACT FROM AUTHOR]

IntroductionFanconi anemia is an autosomal recessive diseasecharacterized by a variety of congenital abnormalities,progressive bone marrow failure,increased chromosomal instability and higherrisk to acute myeloid leukemia, solid tumors. Thisentity can be considered an appropriate biologicalmodel to analyze natural substances with possiblegenotoxic effect. The aims of this study wereto describe and quantify structural chromosomalaberrations induced by 5 flavones, 2 isoflavonesand a topoisomerase II chemotherapeutic inhibitorin Fanconi anemia lymphocytes in order todetermine chromosomal numbers changes and/or type of chromosomal damage.Materials and methodsChromosomes stimulated by phytohaemagglutininM, from Fanconi anemia lymphocytes,were analysed by conventional cytogenetic culture.For each chemical substance and controls,one hundred metaphases were evaluated. Chromosomalalterations were documented by photographyand imaging analyzer. To statisticalanalysis was used chi square test to identify significantdifferences between frequencies of chromosomaldamage of basal and exposed cellcultured a P value less than 0.05.ResultsThere were 431 chromosomal alterations in1000 metaphases analysed; genistein was themore genotoxic bioflavonoid, followed in descendentorder by genistin, fisetin, kaempferol,quercetin, baicalein and miricetin. Chromosomalaberrations observed were: chromatidbreaks, chromosomal breaks, cromatid andchromosomal gaps, quadriratials exchanges,dicentrics chromosome and complex rearrangements.ConclusionBioflavonoids as genistein, genistin and fisetin,which are commonly present in the human diet,showed statistical significance in the number ofchromosomal aberrations in Fanconi anemialymphocytes, regarding the basal damage.

Background: Painters are exposed to an extensive variety of harmful substances like aromatic hydrocarbons used as solvents and paint removers, some of which have shown clastogenic activity. These substances constitute a complex mixture of chemicals which contain well-known genotoxicants, such as Benzene, Toluene and Xylene. Thus, chronic occupational exposure to such substances may be considered to possess genotoxic risk. In Colombia the information available around the genotoxic damage (Chromosomal and DNA damage) in car paint shop workers is limited and the knowledge of this damage could contribute not only to a better understanding of the carcinogenic effect of this kind of substances but also could be used as biomarkers of occupational exposure to genotoxic agents. Results: In this study, the genotoxic effect of aromatic hydrocarbons was assessed in peripheral blood lymphocytes of 24 workers occupationally exposed and 24 unexposed donors, by using Cytogenetic analysis and comet assay. A high frequency of Chromosomal alterations was found in the exposed group in comparison with those observed in the unexposed group. Among the total of CAs observed in the exposed group, fragilities were most frequently found (100 %), followed by chromosomal breaks (58 %), structural (41.2 %) and numerical chromosomal alterations (21 %). Numerical chromosomal alterations, fragilities and chromosomal breaks showed significant differences between exposed and unexposed groups. Among the fragilities, fra(9)(q12) was the most frequently observed. DNA damage index was also significantly higher in the exposed group compared to the unexposed group (p < 0.000). Conclusions: Our results revealed that occupational exposure to aromatic hydrocarbons is significantly associated with Chromosomal and DNA damage in car paint shops workers and are also indicative of high chromosomal instability. The high frequency of both Chromosomal Alterations and DNA Damage Index observed in this study indicates an urgent need of intervention not only to prevent the increased risk of developing cancer but also to the application of strict health control and motivation to the use of appropriate protecting devices during work. [ABSTRACT FROM AUTHOR]

Spent Pot Liner (SPL) is a solid waste from the aluminum industry frequently disposed of in industrial landfills; it can be leached and contaminate the soil, sources of drinking water and plantations, and thus may pose a risk to human health and to ecosystems. Its composition is high variable, including cyanide, fluoride and aluminum salts, which are highly toxic and environmental pollutants. This study evaluated the effect of SPL and its main components on root growth and the mitosis of Lactuca sativa , by investigating the mechanisms of cellular and chromosomal alterations with the aid of immunolocalization. To this end, newly emerged roots of L. sativa were exposed to SPL and its main components (solutions of cyanide, fluoride and aluminum) and to calcium chloride (control) for 48 h. After this, root length was measured and cell cycle was examined by means of conventional cytogenetics and immunolocalization. Root growth was inhibited in the treatments with SPL and aluminum; chromosomal and nuclear alterations were observed in all treatments. The immunolocalization evidenced normal dividing cells with regular temporal and spatial distribution of histone H3 phosphorylation at serine 10 (H3S10ph). However, SPL and its main components inhibited the phosphorylation of histone H3 at serine 10, inactivated pericentromeric regions and affected the cohesion of sister chromatids, thus affecting the arrangement of chromosomes in the metaphase plate and separation of chromatids in anaphase. In addition, these substances induced breaks in pericentromeric regions, characterized as fragile sites. [ABSTRACT FROM AUTHOR]

Background: Primary amenorrhea (PA) is proposed to have multiple etiological factors that include genetic factors, intrauterine malformations, endocrine dysfunction and environmental factors, as revealed by previous studies pertaining to amenorrhea. However, among the various proposed etiologies, genetic factors appear to be highly associated with PA as approximately 40% of PA cases have been found to have genetic causes. Aim of the study: The present study was proposed to establish the frequency and pattern of chromosomal abnormalities in PA cases of Kashmir. Subjects and methods: A total of 108 females within the age group of 14-33 years and having a history of amenorrhea were included in the study. Peripheral blood lymphocyte cultures were set for each subject according to standard protocol and chromosomal analysis was carried out on well spread metaphases by the help of Cytovision software Version 3.9. Results: The results of the present study reveal that the incidence of chromosomal abnormalities in PA cases of this region is almost similar with those of many reports around the world. However, we report two unique chromosomal alterations viz., 46,XX, dup2q(13) and 46,XX, t(2,5)(p11.2;q34) that have not been found elsewhere in the literature. Conclusion: The results of the present study indicate that chromosomal analysis of females with PA, after the exclusion of non-genetic causes, should be essentially considered for the precise diagnosis and the development of more successful treatment. The study being the first of its kind in this part of the world forms the basis for further studies of the PA cases of this region. The precise molecular characterization of the unique breakpoint regions reported in our study can possibly help in the identification of new genes involved in primary amenorrhea. [ABSTRACT FROM AUTHOR]

Chordoma is a rare low-grade primary malignant skeletal tumor, which is presumed to derive from notochord remnants. The pathogenesis of chordoma has not been fully elucidated. However, recent advances in the molecular biology studies have identified brachyury underlying the initiation and progression of chordoma cells. More efforts have been made on accumulating evidence of the notochordal origin of chordoma, discovering signaling pathways and identifying crucial targets in chordomagenesis. In this review, we summarize the most recent research findings and focus on the pathophysiology and molecular mechanisms of chordoma. [ABSTRACT FROM AUTHOR]

Background The purpose of this study was to investigate the cause of behavioral difference between tongue and cheek squamous cell carcinomas (SCCs) by verifying the copy number alterations (CNAs). Methods Array comparative genomic hybridization (aCGH) was used to profile unique deletions and amplifications that are involved with tongue and cheek SCC, respectively. This was followed by pathway analysis relating to CNA genes from both sites. Results The most frequently amplified regions in tongue SCC were 4p16.3, 11q13.4, and 13q34; whereas the most frequently deleted region was 19p12. For cheek SCC, the most frequently amplified region was identified on chromosome 9p24.1-9p23; whereas the most common deleted region was located on chromosome 8p23.1. Further analysis revealed that the most significant unique pathway related to tongue and cheek SCCs was the cytoskeleton remodeling and immune response effect on the macrophage differentiation pathway. Conclusion This study has showed the different genetic profiles and biological pathways between tongue and cheek SCCs. © 2013 Wiley Periodicals, Inc. Head Neck 36: 1268-1278, 2014 [ABSTRACT FROM AUTHOR]

Abstract: Background: Overexpression of the human papillomavirus (HPV) oncogenes E6 and E7 is necessary for the development of distinct lower genital tract cancers. However, secondary cellular genomic alterations are mandatory to promote progression of HPV-induced premalignant stages. We aimed at identifying the chromosomal regions most frequently gained and lost and the disease stage at which the latter occurs. These regions might be relevant for carcinogenesis and could serve as diagnostic markers to identify premalignant lesions with high progression risk towards invasive cancer. Methods: We performed a systematic literature review and meta-analysis of studies listed in PubMed that analysed chromosomal copy number alterations by comparative genomic hybridisation (CGH) in HPV-positive and -negative cancers or premalignant lesions of the anogenital tract (cervix, anus, vagina, penis and vulva). Findings: Data were extracted and analysed from 32 studies. The most common alterations in cervical squamous cell carcinoma (SCC) (12 studies, 293 samples) were gains at 3q with a rate of 0.55 (95% confidence interval (CI) 0.43–0.70), losses at 3p (0.36, 95%CI 0.27–0.48) and losses at 11q (0.33, 95%CI 0.26–0.43). Gains at 3q were particularly frequent in HPV16-positive cervical SCC (0.84, 95%CI 0.78–0.90). Also more than one quarter of high grade cervical intraepithelial neoplasia (CIN) harboured gains of 3q (0.27, 95%CI 0.20–0.36), but the rate in low grade CIN was low (0.02, 95%CI 0.00–0.09). For HPV-associated vulvar SCC (four studies, 30 samples) the same common alterations as in cervical SCC were reported. Studies on non-cervical and non-vulvar SCC and premalignant lesions of the lower genital tract are scarce. Interpretation: 3q gains were most frequently found in HPV16-positive cervical SCC. The results suggest the selection of HPV-transformed cell clones harbouring 3q gains in high grade premalignant lesions, while alterations in low grade lesions are rare. [Copyright &y& Elsevier]

Background: Hepatocellular carcinoma (HCC) is the second leading cause of cancer death in many regions of Asia and the etiology of human HCC is clearly multi-factorial. The development of effective markers for the detection of HCC could have an impact on cancer mortality and significant health implications worldwide. The subjects presented here were recruited based on the serum alpha-fetoprotein level, which is an effective marker for HCC. Further, the chromosomal alterations were elucidated using trypsin G-banding. HCCs with p53 mutations have high malignant potential and are used as an indicator for the biological behavior of recurrent HCCs. The functional polymorphism in the XRCC1 gene, which participates in the base-excision repair of oxidative DNA damage, was associated with increased risk of early onset HCC. Thus, in this investigation, the p53 and XRCC1 gene polymorphisms using the standard protocols were also assessed to find out whether these genes may be associated with HCC susceptibility. Methods: Blood samples from HCC patients ( n = 93) were collected from oncology clinics in South India. Control subjects ( n = 93) who had no history of tumors were selected and they were matched to cases on sex, age, and race. Peripheral blood was analyzed for chromosomal aberrations (CAs) and micronuclei (MN) formation. p53 and XRCC1 genotypes were detected using a PCR-RFLP technique. Results: Specific biomarkers on cytogenetic endpoints might help in diagnosis and treatment measures. The frequencies of genotypes between groups were calculated by χ test. A statistically significant ( p < 0.05) increase in CA was observed in HCC patients compared to their controls as confirmed by ANOVA and MN shows insignificant results. The study on p53 Arg72Pro and XRCC1 Arg399Gln polymorphism in HCC patients demonstrated differences in allele frequencies compared to their controls. Conclusions: The present study indicates that chromosomal alterations and the genetic variations of p53 and XRCC1 may contribute to inter-individual susceptibility to HCC. A very limited role of genetic polymorphism was investigated in modulating the HCC risk, but the combined effect of these variants may interact to increase the risk of HCC in the South Indian population. [ABSTRACT FROM AUTHOR]

Background: Association between DNA alterations and clinical parameters as recurrence, survival or prognosis has been found in a variety of tumors. A clear association between Medullary Thyroid Carcinoma (MTC) and RET oncogene mutation has been accepted. Specifically M918T RET mutation represents the main genetic event in most cases of sporadic MTC (SMTC) and limited chromosomal alterations analyses have been performed. Methods: In the present work, a comparative genomic hybridization (CGH) study was performed using DNA from a primary tumor in a M918T RET mutation-positive SMTC patient and from its lymph node metastasis to investigate additional genetic alterations. We studied a patient with 15 years of follow-up and persistence of disease, confirmed by periodical elevated serum calcitonin (CT) levels. Results: Only 3 chromosomal imbalances were identified in the primary tumor, gain of 18p, and loss of 6p and 16p region, whereas 25 chromosomal imbalances were identified in the metastasis (9 gains and 16 losses). Conclusion: The chromosomal changes 6p-, 16p-, 18p + could determine in part the oncogenic phenotype in the primary M918T RET positive tumor and probably related to persistence of high serum CT levels in this patient. The additional chromosomal changes observed could be related to the metastasis phenotype. We suggest that some genes mapped at 6p, 16p and 18p chromosomal regions, could act as genes associated to cancer and could be related to persistent SMTC and good prognosis. [ABSTRACT FROM AUTHOR]

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Structural variations are widespread in the human genome and can serve as genetic markers in clinical and evolutionary studies. With the advances in the next-generation sequencing technology, recent methods allow for identification of structural variations with unprecedented resolution and accuracy. They also provide opportunities to discover variants that could not be detected on conventional microarray-based platforms, such as dosage-invariant chromosomal translocations and inversions. In this review, we will describe some of the sequencing-based algorithms for detection of structural variations and discuss the key issues in future development. [ABSTRACT FROM AUTHOR]

Congenital heart disease (CHD) is the most common birth defect and the leading cause of mortality in the first year of life. In fetuses with a heart defect, chromosomal abnormalities are very frequent. Besides aneuploidy, 22q11.2 deletion is one of the most recognizable chromosomal abnormalities causing CHD. The frequency of this abnormality varies in nonselected populations. This study aimed to investigate the incidence of the 22q11.2 deletion and other chromosomal alterations in a Brazilian sample of fetuses with structural cardiac anomalies detected by fetal echocardiography. In a prospective study, 68 fetuses with a heart defect were evaluated. Prenatal detection of cardiac abnormalities led to identification of aneuploidy or structural chromosomal anomaly in 35.3% of these cases. None of the fetuses with apparently normal karyotypes had a 22q11.2 deletion. The heart defects most frequently associated with chromosomal abnormalities were atrioventricular septal defect (AVSD), ventricular septal defect (VSD), and tetralogy of Fallot. Autosomal trisomies 18 and 21 were the most common chromosomal abnormalities. The study results support the strong association of chromosome alterations and cardiac malformation, especially in AVSD and VSD, for which a chromosome investigation is indicated. In fetuses with an isolated conotruncal cardiopathy, fluorescence in situ hybridization (FISH) to investigate a 22q11.2 deletion is not indicated. [ABSTRACT FROM AUTHOR]

Background: Colorectal cancer (CRC) is biologically a heterogeneous disease, which may affect response to drug therapy. We investigated the correlation of genome-wide DNA copy number profiles of primary tumors with response to systemic chemotherapy in advanced CRC. [ABSTRACT FROM PUBLISHER]

This study, performed at the behest of ranchers living and working down-prevailing wind from industrial facilities located in Calhoun County, Texas investigated locational risks to ecosystem health associated with proximity to specific industrial complexes. Concerns expressed were for potential genotoxicity in cattle resulting from the release of complex chemical mixtures. The Comet Assay and flow cytometric evaluation of variations in DNA content were utilized to evaluate DNA damage. Bayesian geo-statistical analysis revealed the presence of important spatial processes. The Comet assay's optical density provided a strong indication of increased damage down-prevailing wind from the industrial complexes. Results indicated that proximity to and location down-prevailing winds from industrial facilities increased the locational risk of genotoxicity in this sentinel species. [ABSTRACT FROM AUTHOR]

Some evidences suggest that telomere restriction fragment length (TRF-L) is an effective indicator of histopathogenesis in B-cell tumors. As histopathogenesis is relevant for B-cell chronic lymphocytic leukemia (B-CLL) prognosis, TRF-L was assessed by Southern blot in 201 patients and compared to variable immunoglobulin heave chain gene mutational status (VH-MS) and to other known prognostic features. Overall survival (OS), time to first treatment (TTFT) and progression-free survival (PFS) were evaluated. Our results indicate the following: (1) TRF-L is heterogeneous among B-CLL patients (median 6014 bp, range 1465–16 762); (2) TRF-L correlates to VH-MS (r2=0.1994, P<0.0001) with VH-mutated patients showing long and VH-unmutated short telomeres; however, 41% of VH-unmutated and 5% of VH-mutated patients did not show this correlation and were thus defined as ‘discordant’; (3) TRF-L effectively predicts outcome in terms of TTFT, PFS and OS; (4) VH-unmutated discordant patients have a better clinical outcome than VH-unmutated concordant patients (OS P<0.01, PFS P<0.05) and similar to that of VH-mutated patients (OS, PFS P=NS). Compared to VH-unmutated concordant patients, VH-unmutated discordant patients showed no peculiarity in their immunoglobulin rearrangement nor in their flow cytometry or fluorescence in situ hybridization profile. In conclusion, TRF-L can be helpful to refine prognostication of B-CLL patients, particularly those with a VH-unmutated immunoglobulin sequence.Leukemia (2007) 21, 697–705. doi:10.1038/sj.leu.2404544; published online 15 February 2007 [ABSTRACT FROM AUTHOR]

Abstract: To identify chromosome alterations in Chinese bladder cancer, forty-six transitional cell carcinomas of the bladder were analyzed by comparative genomic hybridization. Frequent gains of DNA copy number were observed on 1p (13/46), 1q (13/46), 5p (8/46), 6p (9/46), 7p (7/46), 8q (12/46), 11q (8/46), 17q (11/46), 19q (7/46), 20q (8/46) and Yq (8/46), with minimal overlapping regions at 1p32-pter (10/46), 1q21-q24 (12/46), 5p (8/46), 6p22-p23 (7/46), 7p11.2-p14 (7/46), 8q22-q24 (12/46), 11q13-q14 (8/46), 17q22-qter (11/46), 19q11-13.2 (7/46), 20q11-q13.2 (8/46) and Yq11 (8/46). Losses were predominantly found on 2q (16/46), 5q (8/46), 8p (7/46), 9p (8/46), 9q (13/46), 11p (7/46), 13q (7/46), 17p (12/46), 18q (7/46), Xp (18/46) and Xq (19/46), with smallest overlapping regions at 2q32-qter (16/46), 5q12-q31 (8/46), 8p12-pter (7/46), 9p21-pter (10/46), 9q (13/46), 11p (7/46), 13q13-q22 (7/46), 17p (12/46), 18q21-qter (7/46), Xp (18/46) and Xq (19/46). There were significantly higher frequencies of gains of 1q21-q24 and 17q22-qter in moderately differentiated tumors as compared with those in well-differentiated tumors, indicating a possible association of these two abnormalities with the dedifferentiation of tumor cells. Gains of 1p32-pter, 5p, 6p22-p23, 11q13-q14, 17q22-qter and losses of 2q32-qter, 9q, 17p were more frequent in pT1 as compared with those in pTa carcinomas. Gains at 1q21-q24, 7p11.2-p14, 8q22-q24, 19q, 20q11-q13.2 and losses at 5q12-q31, 8p12-pter, 9p21-pter, 11p, 13q13-q22 and 18q21-qter were unique to pT1 and higher stage tumors, suggesting that genes responsible for the invasion and progression of bladder cancer might be located at these chromosomal regions. In multiple tumors from the same patients, consistent alterations such as gains of 8q, 11q13-q14, 12q13-q15, 13q12, 20q and losses of 2q32-qter, 8p, 9, 11p, 11q21-qter, 13q13-qter, X were detected. These abnormalities were possibly earlier events, which might play a critical role during the genesis of the tumors. Further detailed studies to the recurrent aberration regions may lead to the identification of oncogenes and tumor suppressor genes involved in the development and progression of Chinese bladder cancer. [Copyright &y& Elsevier]

Abstract: The frequency of chromosomal alterations was compared among four children groups: those with Down syndrome and acute leukemia (DS/AL), those with acute leukemia (AL), those with only Down syndrome (DS) and healthy children (NC). The frequency of acquired chromosome abnormalities was larger in the AL group, followed by the DS/AL. The gaps and isogaps were more frequent in children with only DS. The polymorphisms of the constitutive heterochromatin were larger in the DS/AL group. These findings appear to imply that more genetic changes are necessary to develop AL in the case of healthy children compared to children with DS. [Copyright &y& Elsevier]

Squamous cell carcinoma of the pharynx and larynx (SCCPL) is a genetically complex disease and is frequently associated with nonrandom chromosomal alterations.Fifty primary SCC of the pharynx (oropharynx, n=11, and hypopharynx, n=11) and larynx (n=28) were examined for numerical aberrations of chromosomes 8, 9, 11, and 17 with a panel of chromosome-specific repetitive DNA probes by fluorescence in situ hybridization (FISH). DNA ploidy analysis was also performed by flow cytometry (FCM).Aneusomic copy numbers of chromosomes 8, 9, 11, and 17 were discovered in 66%, 68%, 68% and 78% of tumors, respectively. FCM showed abnormal DNA content in 74% of cases (mean DNA index=1.69). Polysomy was the main finding in both DNA-aneuploid and DNA-diploid tumors (64.5% of cases). Numerical aberrations of chromosomes 8 and 11 correlated to DNA ploidy by FCM (P<0.05). Aneusomy was present in 69.23% of DNA-diploid tumors. Marked intratumoral and intertumoral chromosomal heterogeneity was noted between individual tumors, suggesting a notable heterogeneity in aneuploid and diploid cell populations.Interphase FISH can be used to study important cytogenetic changes which occur during the development of SCC of the pharynx and larynx. [Copyright &y& Elsevier]

Summary. In order fully to identify secondary chromosomal alterations, such as duplications, additions and marker chromosomes that remained unresolved by G banding, 60 cases of t(14;18)-positive follicular lymphoma (FL) were analysed by multicolour karyotyping techniques [multicolour fluorescence in situ hybridization (MFISH)/multicolour banding for chromosome 1 (MBAND1)]. A total of 165 additional structural chromosomal aberrations were delineated. An increased frequency of chromosomal gains involving X, 1q, 2, 3q27-q29, 5, 6p11-p21, 7, 8, 11, 12, 14q32, 17q, 18 and 21 and deletions of 1p36, 3q28-q29, 6q, 10q22-q24 and 17p11-p13 was revealed by the MFISH/MBAND1 analysis. Balanced translocations other than t(14;18) were uncommon, whereas unbalanced translocations were numerous. Deletion of 1p36 and duplication of 1p33-p35, 1p12-p21 and 1q21-q41 were regularly involved in chromosome 1 alterations, seen in 53% of the cases. A strong correlation was demonstrated between gains of individual chromosomal bands and increased gene expression, including 1q22/MNDA , 6p21/CDKN1A , 12q13-q14/SAS , 17q23/ZNF161 , 18q21/BCL2 and Xq13/IL2RG . Unfavourable overall survival was associated with del(1)(p36) and dup(18q). These data support the notion that translocation events are primarily responsible for FL disease initiation, whereas the unbalanced chromosomal gains and losses that mirror the gene expression patterns characterize clonal evolution and disease progression, and thus provide further insights into the biology of FL. [ABSTRACT FROM AUTHOR]

To investigate the chromosomal imbalances that occur in oral carcinoma associated primarily with betel use and their clinical implications, we performed chromosomal analysis using comparative genomic hybridization on 47 patients with this disease. The most common gains of chromosome arms were 8q, 9q and 11q, and the most frequent losses were of chromosomal arms 3p and 4q. The clinical parameters significantly associated with the numbers of chromosomal imbalances per tumor were the age of the patients and nodal metastasis. The preliminary findings of a lower incidence of loss of 4q and gain of 8q in betel-associated tumors compared to non-betel-associated tumors might provide insight into the carcinogenic effect of betel. Deletion of 3p and the gain of 11q alterations were more prevalent in carcinomas with lymph node metastasis than in node-negative tumors, indicating possible loci for metastasis suppressor or metastasis enhancing genes, respectively. Losses of 3p and 4q and gain of 9q were associated with poor outcome for the patients. These data demonstrated that the frequent aberrations in 4q and 9q sites can be used as novel prognostic predictors. [ABSTRACT FROM AUTHOR]

Cancer risk assessment involves the steps of hazard identification, dose-response assessment, exposure assessment, and risk characterization. The rapid advances in the use of molecular biology approaches has had an impact on all 4 components, but the greatest overall current and future impact will be on the dose-response assessment because this requires an understanding of the mechanisms of carcinogenesis, both background and induced by environmental agents. In this regard, hazard identification is a qualitative assessment and dose-response is a quantitative estimate. Thus, the latter will ultimately require a quantitative assessment of molecular endpoints that are used to describe the dose-response for cancer. It has been possible for many years to quantitate alterations at the level of the single gene. For example, analysis of mutation frequency by phenotypic selection, analysis of transcription (mRNA) by Northern blot, analysis of translation (proteins) by Western blot, and analysis of kinetics of metabolism from metabolite levels. However, it is becoming clear that it is necessary when considering risk for adverse health outcomes to develop quantitative approaches for whole cell phenotypes or organ effects. For example, cancer is a whole tissue phenotype, not a feature of single gene mutations, in spite of the multistep (multimutation) mode of formation of a tumor. Thus, there is the need to quantitate the circuitry of a cell: the metabolic/biochemical pathways, genetic regulation pathways, and signaling pathways in normal and stressed conditions. The hypothesis presented by Hanahan and Weinberg of the requirement for 6 acquired characteristics for tumor development, independent of tissue type and species or inducer, seems to provide a viable approach. This hypothesis can be addressed through whole cell molecular assessment using microarrays and quantitative PCR together with the emerging proteomic approaches. This is the world of the new computational cell biology. [ABSTRACT FROM AUTHOR]

Abstract Background Association between DNA alterations and clinical parameters as recurrence, survival or prognosis has been found in a variety of tumors. A clear association between Medullary Thyroid Carcinoma (MTC) and RET oncogene mutation has been accepted. Specifically M918T RET mutation represents the main genetic event in most cases of sporadic MTC (SMTC) and limited chromosomal alterations analyses have been performed. Methods In the present work, a comparative genomic hybridization (CGH) study was performed using DNA from a primary tumor in a M918T RET mutation-positive SMTC patient and from its lymph node metastasis to investigate additional genetic alterations. We studied a patient with 15 years of follow-up and persistence of disease, confirmed by periodical elevated serum calcitonin (CT) levels. Results Only 3 chromosomal imbalances were identified in the primary tumor, gain of 18p, and loss of 6p and 16p region, whereas 25 chromosomal imbalances were identified in the metastasis (9 gains and 16 losses). Conclusion The chromosomal changes 6p-, 16p-, 18p + could determine in part the oncogenic phenotype in the primary M918T RET positive tumor and probably related to persistence of high serum CT levels in this patient. The additional chromosomal changes observed could be related to the metastasis phenotype. We suggest that some genes mapped at 6p, 16p and 18p chromosomal regions, could act as genes associated to cancer and could be related to persistent SMTC and good prognosis. Virtual slides The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1720753793691097

Mitotic cells from Rough lemon ( Citrus jambhiri Lush.), Ohta ponkan ( C. reticulata Blanco) and two somatic hybrid plants obtained from protoplast fusion were analysed by double staining with chromomycin A3 (CMA) and 4′-6-diamidino-2-phenylindole. Only CMA-positive bands were observed in metaphasic chromosomes. The two parental karyotypes (2n=2x=18) were heteromorphic, yielding some marker chromosomes that could be identified in the somatic hybrids. One of the somatic hybrids had 2n=37 chromosomes, and the possible extra chromosome was distinguishable. The second somatic hybrid was tetraploid (2n=4x=36), with one of the chromosomes bearing a putative structural alteration. Furthermore, aneusomaty and some mitotic abnormalities were also observed in this latter plant. Such irregularities are reported for the first time for citrus somatic hybrids, and their possible causes and implications are discussed. [ABSTRACT FROM AUTHOR]

Intracystic papillary tumors of the breast comprise intraductal papillomas and low-grade papillary carcinomas. To determine chromosomal alterations that may be characteristic of these tumors, chromosomes 3, 7, 17 and X were examined in 10 intraductal papillomas and 14 low-grade papillary carcinomas using multicolor fluorescent in situ hybridization. In papillary carcinomas, numerical/structural alterations in chromosome 17 and the accumulation of numerical alterations in chromosomes 3, 7 and X were detected in 21% (3/14) and 15% (2/13) of the cases, respectively. These changes were not detected in papillomas. Loss of chromosome 17p was detected in only one of the 11 DNA-diploid carcinomas, whereas alterations in all four chromosomes were present in a case of DNA-aneuploid carcinoma. Numerical alterations of chromosomes 3, 7, 17 and X do not appear to be involved in the development of low-grade papillary carcinomas with DNA diploidy, but rather accumulate during the formation of DNA-aneuploid carcinoma cells in association with other chromosome alterations. [ABSTRACT FROM AUTHOR]

FADD was initially described as an adaptor molecule for death receptor-mediated apoptosis, but subsequently it has been implicated in nonapoptotic cellular processes such as proliferation and cell cycle control. During the last decade, FADD has been shown to play a pivotal role in most of the signalosome complexes, such as the necroptosome and the inflammasome. Interestingly, various mechanisms involved in regulating FADD functions have been identified, essentially posttranslational modifications and secretion. All these aspects have been thoroughly addressed in previous reviews. However, FADD implication in cancer is complex, due to pleiotropic effects. It has been reported either as anti- or protumorigenic, depending on the cell type. Regulation of FADD expression in cancer is a complex issue since both overexpression and downregulation have been reported, but the mechanisms underlying such alterations have not been fully unveiled. Posttranslational modifications also constitute a relevant mechanism controlling FADD levels and functions in tumor cells. In this review, we aim to provide detailed, updated information on alterations leading to changes in FADD expression and function in cancer. The participation of FADD in various biological processes is recapitulated, with a mention of interesting novel functions recently proposed for FADD, such as regulation of gene expression and control of metabolic pathways. Finally, we gather all the available evidence regarding the clinical implications of FADD alterations in cancer, especially as it has been proposed as a potential biomarker with prognostic value. [ABSTRACT FROM AUTHOR]