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Complex chromosomal aberrations in bone marrow cells of adult patients with myelodysplastic syndromes (MDS): frequency, mechanism of origin and clinical significance.
Rochlová, Kristina ; Zemanová, Zuzana (advisor) ; Novotná, Drahuše (referee)
Complex chromosomal aberrations occurs are described in approximately 20 % of patients with myelodysplastic syndrome (MDS) and are associated with a poor prognosis. Nevertheless, the mechanism and possible causes responsible for the emergence of these aberrations are not fully understood. There are two models describing the emergence of these aberrations, namely shattering of single chromosomes or their parts during the so-called cellular crisis (chromothripsis) and/or progressive accumulation of chromosomal aberrations during the course of the disease (clonal evolution). Using combination of cytogenomic methods we examined 61 samples of bone marrow from adult patients with MDS and a complex karyotype. Unbalanced aberrations with loss of genetical material were found in most cases. Chromosomes 5, 7 and 12 were most frequently involved in rearrangements. Clonal development, chromothripsis and both mechanism was detected in 26, 12 and 14 patients, respectively. Patients with deleted chromosome 5 included in complex karyotype had the shortest overall survival. The cause of emergence of complex aberrations did not affect survival. Cytogenomic analysis of complex aberrations allows detection of balanced and unbalanced changes and identification of important processes of tumorigenesis such as clonal...
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Males-females differences in the spectrum of chromosomal aberrations in the group of nanocomposites production workers
Rössnerová, Andrea ; Pelcová, D. ; Ždímal, Vladimír ; Elzeinova, Fatima ; Margaryan, Hasmik ; Chvojková, Irena ; Topinka, Jan ; Schwarz, Jaroslav ; Ondráček, Jakub ; Koštejn, Martin ; Komarc, M. ; Vlčková, Š. ; Fenclová, Z. ; Lischková, L. ; Dvořáčková, Š. ; Rössner ml., Pavel
An increase in the use of nanomaterials (NM) has been witnessed in many areas of human life. Therefore, assessment of genotoxicity of NM and nanoparticles (NP) is one of the main objectives of genetic toxicology. Despite this fact, human cytogenetic studies following the exposure to NP are still rare. Moreover, no relevant information on possible differences in sensitivity to NP related to gender is available.\n\nIn this study we periodically (in September 2016, 2017 and 2018; pre-shift and post-shift each year) analyzed a group of workers (both genders), working long time in nanocomposites research, and matched controls. Aerosol exposure monitoring of particulate matter including nano-sized fractions was carried out during working shift. Micronucleus assay using Human Pan Centromeric probes, was applied to distinguish, besides the frequency of total MN in binucleated cells (BNC), also other types of chromosomal damage (losses and breaks). Moreover, whole-chromosome painting (WCP) for autosome #1 and both gonosomes (X and Y) were applied in third sampling period (2018) with the aim to identify the particular structural and numerical chromosomal aberrations.\n\nObtained results showed: (i) differences in the risk of exposure to NP related to individual working processes (welding, smelting and machining); (ii) differences in chemical composition of nano-fraction; (iii) no effect of chronic exposure of NP (total MN) opposite to significant effect of acute exposure; (iv) gender-related DNA damage differences (females seem to be more sensitive to chromosomal losses). Additional data from WCP suggested increased frequency of numerical aberrations in gonosomes.
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Acquired chromosomal aberrationns in peripheral blood lymphocytes of patients with newly diagnosed cancer and healthy control individuals.
Vodenková, Soňa ; Polívková, Zdeňka (advisor) ; Langová, Martina (referee)
The majority of human cancers arise due to cells inabitily to maintain genomic stability. Cytogenetic changes (especially chromosomal aberrations) in peripheral blood lymphocytes which reflect not only the individual exposure to genotoxic factors, but also individual sensitivity to genotoxic effect and the tumor is late consequence to genotoxic effect. Summary epidemiological prospective studies over the last ten years have shown that increased level of chromosomal aberrations in peripheral blood lymphocytes is predictive of cancer risk. This thesis is focused on the detection of particular types of chromosomal damage in patients with choosed types of newly diagnosed cancers compared to healthy control persons. We cytogenetically analyzed 100 patients with colorectal cancer and 298 controls and 123 patients with breast cancer and 123 controls - healthy women. We compared the percentage of aberrant cells, the percentage of total aberrations, the percentages of chromatid and chromosome aberrations found in patients with both types of tumors and in controls and we verified the predictive value of chromosomal aberrations as a biomarker of cancer risk. In patients with colorectal cancer was statistically significantly increased only the level of chromatid aberrations (CHTA) (1,45±1,28) compared to...
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Role of chromosomal aberrations to evaluate genetic risk of exposure to carcinogens.
Rössnerová, Andrea ; Šrám, Radim (advisor) ; Rubeš, Jiří (referee) ; Kuglík, Petr (referee)
(in English) Air pollution is a serious worldwide problem associated with the risk of cancer. The negative effect of carcinogenic polycyclic aromatic hydrocarbons (c-PAHs), including benzo[a]pyrene (B[a]P), on human health is analyzed using specific biomarkers. Among them biomarkers of early effect play an important role. This work summarizes the results of cytogenetic analyses performed by fluorescence in situ hybridization (FISH) (whole chromosome painting of chromosomes #1 and #4) and automated image analysis of micronuclei (MN). During the analyses a total set of 1304 samples was analyzed by the FISH method and 885 samples by the automated image analysis of MN. Studied groups including city policemen, garage men, bus drivers, administrative workers, mothers, newborns, healthy children and children with bronchial asthma and laboratory workers were from Prague, Ostrava and Ceske Budejovice. The locations significantly differed in levels of air pollutants and the type of air pollution. The exposure of participants of the study was assessed by personal and stationary monitoring. The impact of other factors including age, smoking or intake of vitamins was also evaluated in these studies. The results obtained by the FISH method in Prague showed the impact of seasonal variability of concentrations of...
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Developmental defects and their examination in biochemical screening
TOMANOVÁ, Andrea
This thesis deals with the issue of congenital developmental defects, with the focus on the most frequently occurring chromosomal aberrations. The main focus is biochemical screening of pregnant women as an integral part of prenatal diagnostics. The aim is to produce summary statistics of the occurrence of the three most frequent chromosomal aberrations based on acquired data and to compare the results with the official statistics of the occurrence of these anomalies within the Czech Republic.
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Chromosomal aberrations in childhood acute leukemia.
Sládková, Lucie ; Zemanová, Zuzana (advisor) ; Šárová, Iveta (referee)
1 Abstract Leukemias are the most common cancer diseases in childhood. The majority of cases represent acute leukemias, the most common of which is acute lymphoblastic leukemia (ALL), the second most frequent subtype is acute myeloid leukemia (AML). One of the basic laboratory examinations at the time of diagnosis is the cytogenetic analysis of the karyotype of leukemic cells in which we are looking for the recurrent chromosomal aberrations. These changes in the structure or number of the chromosomes can be found in up to 90 % of patients and the exact prognostic significance is known for most of them. In ALL, the findings of high hyperdiploidy (>50 chromosomes) and translocation t(12;21)(p13;q22) are considered the most significant prognostic factor associated with good prognosis and translocations involving the KMT2A gene in the 11q23 region are associated with poor prognosis. In AML, the most frequent aberrations are t(8;21)(q22;q22), t(15;17)(q24;q21) and inv(16)(p13;q22) which are considered indicator of good prognosis. An important unfavourable prognostic finding in AML are the KMT2A gene rearrangements, the most common of which is the translocation t(9;11)(q23;p13.1). Nowadays, there are many ways to detect chromosomal aberrations in leukemic cells. G-banding is the most common method of classical...
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Application of cytogenetic and molecular cytogenetic methods in prenatal diagnosis
Rašpličková, Tereza ; Novotná, Drahuše (advisor) ; Zemanová, Zuzana (referee)
Foetal anomalies found on ultrasound increase the probability of occurrence of chromosomal abnormalities. They cause about one quarter of all abortions and stillbirths and many of inborn defects in newborns. Karyotype analysis is number one method in prenatal diagnosis whereas array CGH is often used as a verification and supplemental method. The aim of this work was to prove that array CGH gives additional chromosomal findings to karyotypes and could substitute conventional karyotyping as a primary examination method in foetuses with ultrasound findings. We examined 45 prenatal samples using both methods. These samples were referred for invasive examination because of abnormal ultrasound findings. Karyotype analyses found two abnormalities in two (4,4 %) patients and array CGH identified aberrations in five (11,1 %) foetuses whereas both anomalies detected by karyotypes were discovered by array CGH too. This means that array CGH identified about 6,7 % more aberrations than karyotype. Our results correspond with scientific articles which refer that array CGH should replace karyotype not only in postnatal examinations but even in prenatal diagnosis. Keywords: chromosomal aberrations, array CGH, karyotype, prenatal diagnosis, ultrasound
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Acquired chromosomal aberrationns in peripheral blood lymphocytes of patients with newly diagnosed cancer and healthy control individuals.
Vodenková, Soňa ; Polívková, Zdeňka (advisor) ; Langová, Martina (referee)
The majority of human cancers arise due to cells inabitily to maintain genomic stability. Cytogenetic changes (especially chromosomal aberrations) in peripheral blood lymphocytes which reflect not only the individual exposure to genotoxic factors, but also individual sensitivity to genotoxic effect and the tumor is late consequence to genotoxic effect. Summary epidemiological prospective studies over the last ten years have shown that increased level of chromosomal aberrations in peripheral blood lymphocytes is predictive of cancer risk. This thesis is focused on the detection of particular types of chromosomal damage in patients with choosed types of newly diagnosed cancers compared to healthy control persons. We cytogenetically analyzed 100 patients with colorectal cancer and 298 controls and 123 patients with breast cancer and 123 controls - healthy women. We compared the percentage of aberrant cells, the percentage of total aberrations, the percentages of chromatid and chromosome aberrations found in patients with both types of tumors and in controls and we verified the predictive value of chromosomal aberrations as a biomarker of cancer risk. In patients with colorectal cancer was statistically significantly increased only the level of chromatid aberrations (CHTA) (1,45±1,28) compared to...
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Role of chromosomal aberrations to evaluate genetic risk of exposure to carcinogens.
Rössnerová, Andrea ; Šrám, Radim (advisor) ; Rubeš, Jiří (referee) ; Kuglík, Petr (referee)
(in English) Air pollution is a serious worldwide problem associated with the risk of cancer. The negative effect of carcinogenic polycyclic aromatic hydrocarbons (c-PAHs), including benzo[a]pyrene (B[a]P), on human health is analyzed using specific biomarkers. Among them biomarkers of early effect play an important role. This work summarizes the results of cytogenetic analyses performed by fluorescence in situ hybridization (FISH) (whole chromosome painting of chromosomes #1 and #4) and automated image analysis of micronuclei (MN). During the analyses a total set of 1304 samples was analyzed by the FISH method and 885 samples by the automated image analysis of MN. Studied groups including city policemen, garage men, bus drivers, administrative workers, mothers, newborns, healthy children and children with bronchial asthma and laboratory workers were from Prague, Ostrava and Ceske Budejovice. The locations significantly differed in levels of air pollutants and the type of air pollution. The exposure of participants of the study was assessed by personal and stationary monitoring. The impact of other factors including age, smoking or intake of vitamins was also evaluated in these studies. The results obtained by the FISH method in Prague showed the impact of seasonal variability of concentrations of...
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