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1.
Medicine (Baltimore) ; 99(40): e22532, 2020 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-33019458

RESUMO

RATIONALE: Small supernumerary marker chromosomes (sSMC) are structurally abnormal chromosomes, which can be detected in patients with developmental retardation, infertile problems, and prenatal fetus. We report 3 adult female with fertility problems carrying sSMC(14/22) and aim to explore the correlation between sSMC(14/22) and fertility problems in women. PATIENT CONCERNS: Three Chinese female patients were referred for infertility consultation in our hospital. DIAGNOSES: The karyotype of these 3 patients were 47, XX, +mar. The chromosome microarray analysis (CMA) detected various chromosomal duplications and deletions in the 3 cases: a 0.49Mb gain of 5q32 for case 1; a 0.54Mb gain of 14q32.33 and a 1.83Mb gain of 16p11.2 for case 2; a 0.37Mb loss of 13q21.2q21.31 and a 0.12Mb gain of Xp11.2 for case 3. Fluorescence in situ hybridization (FISH) using the specific probes for chromosomes 13/21, 14/22, and 15 was applied to identify the origination of these sSMC, which were all finally identified as sSMC(14/22). INTERVENTIONS: Case 1 underwent the artificial reproductive technology to get her offspring and finally delivered a healthy male infant at 39 weeks. Case 2 did not plan to choose in vitro fertilization (IVF) to get offspring. Case 3 refused to do assisted reproductive technology. OUTCOMES: The genotype-phenotype correlation of sSMC(14/22) remain unclear. However, the existence of sSMC(14/22) might negatively affect the fertility ability in sSMC female carriers. LESSONS: The combined application of traditional banding technique and molecular cytogenetic techniques can better identify more details of sSMC. For sSMC carriers with fertility problems, they could get their offsprings through assisted reproductive technologies after comprehensive fertility assessment.


Assuntos
Aberrações Cromossômicas , Cromossomos Humanos Par 14/genética , Cromossomos Humanos Par 22/genética , Infertilidade Feminina/genética , Adulto , China , Duplicação Cromossômica , Análise Citogenética , Feminino , Humanos , Hibridização in Situ Fluorescente , Cariótipo
2.
Nat Commun ; 11(1): 4374, 2020 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-32873787

RESUMO

Oncogene amplification, a major driver of cancer pathogenicity, is often mediated through focal amplification of genomic segments. Recent results implicate extrachromosomal DNA (ecDNA) as the primary driver of focal copy number amplification (fCNA) - enabling gene amplification, rapid tumor evolution, and the rewiring of regulatory circuitry. Resolving an fCNA's structure is a first step in deciphering the mechanisms of its genesis and the fCNA's subsequent biological consequences. We introduce a computational method, AmpliconReconstructor (AR), for integrating optical mapping (OM) of long DNA fragments (>150 kb) with next-generation sequencing (NGS) to resolve fCNAs at single-nucleotide resolution. AR uses an NGS-derived breakpoint graph alongside OM scaffolds to produce high-fidelity reconstructions. After validating its performance through multiple simulation strategies, AR reconstructed fCNAs in seven cancer cell lines to reveal the complex architecture of ecDNA, a breakage-fusion-bridge and other complex rearrangements. By reconstructing the rearrangement signatures associated with an fCNA's generative mechanism, AR enables a more thorough understanding of the origins of fCNAs.


Assuntos
Amplificação de Genes , Genômica/métodos , Neoplasias/genética , Oncogenes/genética , Linhagem Celular Tumoral , Mapeamento Cromossômico/métodos , Análise Citogenética , Genoma Humano/genética , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Humanos
3.
Georgian Med News ; (304-305): 141-147, 2020.
Artigo em Russo | MEDLINE | ID: mdl-32965265

RESUMO

Objective - to study the ability of N-oxide-2,6-dimethylpyridine to modify the cytogenetic effects in mouse bone marrow cells caused by an alkylating antitumor cytostatic cyclophosphamide.; The cytogenetic activity and mutagen-modifying effect of the plant growth regulator N-oxide-2,6-dimethylpyridine (Ivin) were studied by the method of accounting for chromosomal aberrations in the bone marrow cells of CD-1 mice (males) with a single joint exposure to cyclophosphamide. In the first variant of the research, Ivin was administered single orally in the form of an aqueous solution at doses of 710, 71, 7.1, 0.7, and 0.07 mg/kg bw, which corresponds to 1/2, 1/20, 1/200, 1/2000 and 1/20000 from LD50. In the second variant - Ivin was administered together with Cyclophosphamide (Ivin - in the same way as in the first research variant, cyclophosphamide was administered intraperitoneally at a dose of 40 mg/kg bw the same as the positive control group). Intact animals (negative control group) were orally administered purified, UV-sterilized, deionized water.; It was shown that with isolated administration of Ivin in the studied doses did not show mutagenic activity. When combined with Cyclophosphamide, Ivin at a dose of 710 mg/kg bw did not induce the frequency of metaphases with chromosome aberrations and at a dose of 71 mg/kg bw reduced the frequency of metaphases with chromosome aberrations by 1.8 times in comparison with the positive control. In both of these dose groups, Ivin reduced the number of chromatid-type aberrations and polyploid cells but increased the number of multi-aberrant cells. This is probably due to the additional chemical load and physicochemical state of the Ivin molecule. When combined with Cyclophosphamide, Ivin at low dose levels (7.1, 0.7 and 0.07 mg/kg bw) significantly reduced the frequency of metaphases with chromosome aberrations (by 55.7%, 62.9% и 72.9%, respectively), the amount of chromatid-type aberrations, polyploid, and multi-aberrant cells. This may be due to the gene protective effect of Ivin, because of the stabilization of membranes and its antioxidant effect.


Assuntos
Células da Medula Óssea , Aberrações Cromossômicas , Animais , Ciclofosfamida/toxicidade , Análise Citogenética , Masculino , Óxidos
4.
PLoS One ; 15(9): e0239377, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32986735

RESUMO

Double pollen fertility neutral genes, San and Sbn, can control pollen sterility in intersubspecific (indica × japonica) rice hybrids, which has excellent potential to increase rice yield. Previous studies showed that polyploidy could increase the interaction of three pollen sterility loci, i.e. Sa, Sb and Sc, which cause pollen sterility in autotetraploid rice hybrids, and hybrid fertility could be improved by double neutral genes, San and Sbn, in autotetraploid rice hybrids. We compared cytological and transcriptome data between autotetraploid and diploid rice hybrid during meiosis and single microspore stages to understand the molecular mechanism of neutral genes for overcoming pollen sterility in autotetraploid rice hybrids, which harbored double neutral genes. Cytological results revealed that the double neutral genes resulted in higher pollen fertility (76.74%) and lower chromosomal abnormalities in autotetraploid hybrid than in parents during metaphase I, metaphase II, anaphase I and anaphase II. Moreover, autotetraploid rice hybrid displayed stronger heterosis than a diploid hybrid. Compared with diploid rice hybrid, a total of 904 and 68 differently expressed genes (DEGs) were identified explicitly in autotetraploid hybrid at meiosis and single microspore stages, respectively. Of these, 133 and 41 genes were detected in higher-parent dominance and transgressive up-regulation dominance, respectively, which were considered autotetraploid potential heterosis genes, including a meiosis-related gene (Os01g0917500, MSP1) and two meiosis specific-genes (Os07g0624900 and Os04g0208600). Gene Ontology (GO) and Kyoto Encyclopedia of Gene and Genomes pathway (KEGG) analysis revealed that DEGs significantly enriched in amino acid metabolism and photosynthesis metabolism. These results indicated that meiosis-specific and meiosis-related genes, and amino acids and photosynthesis metabolism-related genes contribute to higher yield and pollen fertility in autotetraploid rice hybrid. This study provides a theoretical basis for molecular mechanisms of heterosis in autotetraploid rice harboring double neutral genes for pollen fertility.


Assuntos
Análise Citogenética , Diploide , Perfilação da Expressão Gênica , Genes de Plantas/genética , Oryza/genética , Tetraploidia , Cromossomos de Plantas/genética , Fenótipo , Infertilidade das Plantas/genética , Pólen/genética , Pólen/fisiologia
5.
Mutat Res ; 856-857: 503220, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32928367

RESUMO

We assessed the radioprotective and mitigative actions of sodium diclofenac, a non-steroidal anti-inflammatory drug using cultured human peripheral blood as a model. Both pre- and post-irradiation treatments with the drug reduced gamma radiation-induced formation of dicentric chromosome, cytochalasin-blocked micronuclei and γ-H2AX foci in human peripheral blood lymphocytes. This work supports the concept that sodium diclofenac may be a useful radiation countermeasure agent.


Assuntos
Diclofenaco/farmacologia , Relação Dose-Resposta à Radiação , Histonas/genética , Protetores contra Radiação/farmacologia , Proliferação de Células/efeitos dos fármacos , Proliferação de Células/efeitos da radiação , Aberrações Cromossômicas/efeitos dos fármacos , Aberrações Cromossômicas/efeitos da radiação , Análise Citogenética/métodos , Reposicionamento de Medicamentos , Raios gama/efeitos adversos , Regulação da Expressão Gênica/efeitos dos fármacos , Regulação da Expressão Gênica/efeitos da radiação , Humanos , Peroxidação de Lipídeos/efeitos dos fármacos , Peroxidação de Lipídeos/efeitos da radiação , Linfócitos/efeitos dos fármacos , Linfócitos/efeitos da radiação
6.
Ann Biol Clin (Paris) ; 78(5): 483-491, 2020 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-32933889

RESUMO

OBJECTIVE: Principal objective of this work was to analyse the cost effectiveness of different sequences of cytogenetic techniques from the hospital's point of view, after prenatal ultrasound has identified fetal malformations. METHODS: Cytogenetic tests were performed for each case in 3 strategies, and their results are reported and compared to one reference strategy. Two new simulated strategies were considered: chromosomal microarrays alone and a direct test + CMA. MAIN OUTCOMES MEASURES: cost-effectiveness ratio. RESULTS: A single test result was positive in 234 of the 835 pregnancies studied (28%). CMA alone would have identified 239 abnormalities. In the simulated direct test + CMA sequence, the direct test alone would have been positive for 66.1% of the abnormalities identified. When testing was indicated for NT, reference strategy (Direct + karyotyping) costs 1 084.8 euros by positive test results. Strategies Direct + CMA and CMA alone cost respectively 992.7 and 550.0 euros by positive test results. For OUM indications, reference strategy costs 2 937.8 euros by positive test results. Strategies Direct + CMA and CMA alone cost respectively, 2 118.4 and 1 304.7 euros by positive test results. CONCLUSIONS: CMA appears to be the most effective test for prenatal cytogenetic diagnosis of fetal abnormalities identified by ultrasound.


Assuntos
Aberrações Cromossômicas , Doenças Fetais/diagnóstico , Feto/anormalidades , Diagnóstico Pré-Natal/economia , Diagnóstico Pré-Natal/métodos , Ultrassonografia Pré-Natal , Adulto , Algoritmos , Análise Custo-Benefício , Análise Citogenética/economia , Análise Citogenética/métodos , Árvores de Decisões , Feminino , Doenças Fetais/genética , Feto/diagnóstico por imagem , França , Humanos , Cariotipagem/economia , Cariotipagem/métodos , Valor Preditivo dos Testes , Gravidez , Estudos Retrospectivos , Ultrassonografia Pré-Natal/economia
7.
Anim Sci J ; 91(1): e13440, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-32885569

RESUMO

Cytogenetic tests are used to assess the influence of physical and chemical factors with potential mutagenic and genotoxic properties on the animal organism. The test results make it possible to eliminate mutagens, as well as helping predict possible genetic consequences in animal cells and assess animal resistance. The aim of this study was to examine, using cytogenetic tests, the spontaneous chromosome and DNA damage in coypu lymphocytes. Four tests: fragile site (FS), bleomycin (BLM), micronucleus, (MN) and comet were used for the first time in coypu cells. The averages with standard deviations obtained in the research were as follows: 3.30 ± 0.80 fragile sites/cell; 0.63 ± 0.80 BLM damage/cell; 6.10 ± 0.53% binucleated cells with MN; and 3.24 ± 0.63% DNA in tail. The present analysis showed high interindividual variation in spontaneous chromosomal and DNA damage levels. In the case of micronucleus, fragile sites, and comet assays, the differences between animals were statistically significant. The data suggest that these assays are sensitive enough to detect some effects on an individual animal and can be proposed as tools for coypu biomonitoring.


Assuntos
Monitoramento Biológico/métodos , Variação Biológica Individual , Análise Citogenética/métodos , Análise Citogenética/veterinária , Roedores/genética , Animais , Bleomicina , Aberrações Cromossômicas/veterinária , Sítios Frágeis do Cromossomo , Ensaio Cometa/veterinária , Dano ao DNA , Feminino , Linfócitos , Micronúcleos com Defeito Cromossômico
8.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 28(4): 1272-1277, 2020 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-32798411

RESUMO

OBJECTIVE: To explore the renal pathology and cytogenetic features in the multiple myeloma (MM) patients with renal impairment. METHODS: The clinical data of newly diagnosed MM patients with renal impairment in our hospital from January 2009 to January 2019 were analyzed retrospectively, and the relationship between FISH results and results of renal pathological exanimation was analyzed statistically by using SPSS 20.0. RESULTS: A total of 20 patients underwent renal biopsy, included 12 males and 8 females. FISH result showed that out of 20 patients, 7 cases presented interstitial nephritis, among which 3 cases were negative for FISH, and in the remaining cases the rate of IgH rearrangement, 1q21 amplification, RB1 deletion, D13S319 deletion, and P53 deletion detection was 42.86%, 28.57%, 28.57%, 28.57% and 14.29% respectively, the detection positive rate was statistically significantly lower as compared with total probe positive rate (P<0.01). There were 6 cases of cast nephropathy, among which IgH rearrangement, the rate of 1q21 amplification, RB1 deletion, D13S319 deletion, and P53 deletion detection was 66.67%, 50%, 66.67%, 50% and 0% respectively. Compared with the total probe positive rate, there was no statistical significance (P>0.05). There were 4 cases of acute tubular necrosis, among which the detection rates of IgH rearrangement, 1q21 amplification, RB1 deletion, D13S319 deletion, and P53 deletion was 100%, 50%, 50%, 25% and 25%, respectively. Compared with the total probe positive rate, there was no statistical significance (P>0.05). There were one case of amyloidosis, and one case of tubular nephropathy with amyloidosis, the detection with 5 probes were all positive. One case of light chain deposition disease was positive for RB1 gene deletion + D13S319 gene deletion. CONCLUSION: FISH in the MM patients with different renal pathological changes is characterized by heterogeneity, which can be used to predict the risk of renal damage and speculate possible renal pathological types to guide prognosis.


Assuntos
Mieloma Múltiplo , Aberrações Cromossômicas , Análise Citogenética , Citogenética , Feminino , Humanos , Hibridização in Situ Fluorescente , Masculino , Estudos Retrospectivos
9.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi ; 37(8): 867-870, 2020 Aug 10.
Artigo em Chinês | MEDLINE | ID: mdl-32761597

RESUMO

OBJECTIVE: To explore the genetic basis for a child with developmental delay and mental retardation. METHODS: Chromosomal karyotype of the child was analyzed by G-, C- and N-banding techniques. Her genome DNA was analyzed with single nucleotide polymorphisms array (SNP array). The result was validated by fluorescence quantitative polymerase chain reaction (PCR). RESULTS: The karyotype of the child was ascertained as 46,XX,r(22)(p12q13). SNP array has revealed a deletion of approximately 1.4 Mb at 22q13.33 (49 802 963-51 197 766). The deletion has encompassed the SHANK3, a crucial gene for the development of nervous system. Fluorescence quantitative PCR has confirmed the deletion of exons 7, 19 and 22 of the SHANK3 gene. CONCLUSION: The phenotype of the patient may be attributed to the microdeletion at 22q13.33. Cytogenetic methods combined with SNP array and fluorescence quantitative PCR can identify aberrant chromosomes and provide accurate information for the clinical diagnosis and genetic counseling.


Assuntos
Análise Citogenética , Deficiências do Desenvolvimento/genética , Deficiência Intelectual , Criança , Bandeamento Cromossômico , Deleção Cromossômica , Cromossomos Humanos Par 22 , Feminino , Humanos , Deficiência Intelectual/genética , Cariotipagem , Polimorfismo de Nucleotídeo Único
10.
PLoS Biol ; 18(8): e3000817, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32813728

RESUMO

During meiosis, chromosomes adopt a specialized organization involving assembly of a cohesin-based axis along their lengths, with DNA loops emanating from this axis. We applied novel, quantitative, and widely applicable cytogenetic strategies to elucidate the molecular bases of this organization using Caenorhabditis elegans. Analyses of wild-type (WT) chromosomes and de novo circular minichromosomes revealed that meiosis-specific HORMA-domain proteins assemble into cohorts in defined numbers and co-organize the axis together with 2 functionally distinct cohesin complexes (REC-8 and COH-3/4) in defined stoichiometry. We further found that REC-8 cohesins, which load during S phase and mediate sister-chromatid cohesion, usually occur as individual complexes, supporting a model wherein sister cohesion is mediated locally by a single cohesin ring. REC-8 complexes are interspersed in an alternating pattern with cohorts of axis-organizing COH-3/4 complexes (averaging 3 per cohort), which are insufficient to confer cohesion but can bind to individual chromatids, suggesting a mechanism to enable formation of asymmetric sister-chromatid loops. Indeed, immunofluorescence/fluorescence in situ hybridization (immuno-FISH) assays demonstrate frequent asymmetry in genomic content between the loops formed on sister chromatids. We discuss how features of chromosome axis/loop architecture inferred from our data can help to explain enigmatic, yet essential, aspects of the meiotic program.


Assuntos
Caenorhabditis elegans/genética , Proteínas de Ciclo Celular/genética , Cromátides/ultraestrutura , Proteínas Cromossômicas não Histona/genética , Cromossomos/ultraestrutura , Meiose , Complexo Sinaptonêmico/ultraestrutura , Animais , Caenorhabditis elegans/metabolismo , Proteínas de Caenorhabditis elegans/genética , Proteínas de Caenorhabditis elegans/metabolismo , Proteínas de Ciclo Celular/metabolismo , Cromátides/metabolismo , Proteínas Cromossômicas não Histona/metabolismo , Segregação de Cromossomos , Cromossomos/metabolismo , Análise Citogenética , Hibridização in Situ Fluorescente , Fase S/genética , Complexo Sinaptonêmico/metabolismo
12.
Artigo em Inglês | MEDLINE | ID: mdl-32684077

RESUMO

Plant models may be useful as test organisms for initial screening of potential toxicity of personal care products. The objective of the present study was to assess the efficacy of the Allium cepa (common onion) test system as a bioanalytical tool for screening potential cytotoxicity and genotoxicity of herbal-based hair dye formulations. Exposure of black hair dye formulations for 48 hours resulted in root growth retardation and mitosis suppression in the root meristems of A. cepa bulbs indicating concentration dependent cytotoxicity. At the 72 hour post exposure, cytotoxic effects on the roots were reduced but not recovered completely signifying prolong toxic action of the hair dyes. The condensed nuclei was the most frequent nuclear abnormality found in the dye exposed root meristematic cells indicating the cell death process. Induction of micronuclei and chromosomal aberrations in the root meristematic cells even at the post exposure stage indicates persistent genotoxicity of the hair dyes which may be attributed to the interactive effects of chemical mixtures present in the commercial hair dye formulations. The results revealed that A. cepa test system is an effective bioanalytical tool for screening cytogenotoxicity of commercial hair dye formulations.


Assuntos
Tinturas para Cabelo/farmacologia , Cebolas/efeitos dos fármacos , Aberrações Cromossômicas , Análise Citogenética , Dano ao DNA , Meristema/efeitos dos fármacos , Mitose , Cebolas/citologia , Cebolas/genética , Raízes de Plantas/efeitos dos fármacos
13.
Int J Hematol ; 112(5): 728-733, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32519173

RESUMO

Few hematological complications have previously been reported in association with Cri du Chat syndrome (CdCS). A case of myelodysplastic syndromes (MDS) in a pediatric patient with CdCS is herein presented. A 17-year-old female with CdCS caused by ring chromosome 5 was admitted to the hospital for investigation of a 1-month history of anemia. Based on the morphological findings of bone marrow, the patient was diagnosed with refractory cytopenia with multilineage dysplasia. The risk group was classified as intermediate-1 in the International Prognostic Scoring System (IPSS), and low in the revised IPSS. Assessment by microarray comparative genomic hybridization (CGH) identified the breakpoints of ring chromosome 5 as 46,XX,r(5)(p14.3q35.3). This revealed that the 5q terminal deletion did not include the common deleted region of MDS with del(5q). Treatment with azacitidine was initiated to control disease progression and improve quality of life. At baseline, the patient had a mean transfusion requirement of 3 units/month, which decreased to 2 units/month after six cycles of azacitidine and to 1 unit/month after 10 cycles of azacitidine. Cytopenia observed in the presented case seemed irrelevant to ring chromosome 5 which is the causative cytogenetic abnormality of CdCS, and further analyses may be needed to clarify the pathogenesis.


Assuntos
Azacitidina/administração & dosagem , Deleção Cromossômica , Cromossomos Humanos Par 5/genética , Síndrome do Miado do Gato/genética , Síndromes Mielodisplásicas/tratamento farmacológico , Síndromes Mielodisplásicas/etiologia , Síndromes Mielodisplásicas/genética , Cromossomos em Anel , Adolescente , Fatores Etários , Síndrome do Miado do Gato/etiologia , Análise Citogenética/métodos , Feminino , Humanos , Síndromes Mielodisplásicas/sangue , Qualidade de Vida , Resultado do Tratamento
14.
PLoS One ; 15(6): e0234331, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32525943

RESUMO

The hyline tribe Lophyohylini includes 87 species of treefrogs, of which cytogenetics aspects have been studied in less than 20% of them. In order to evaluate the evolution of some of its chromosome characters (NOR position, C-bands, and DAPI/CMA3 bands), we studied the karyotypes of 21 lophyohylines, 16 of them for the first time, and analyzed them in a phylogenetic context. Most species showed similar karyotypes regarding chromosome number (2n = 24) and morphology (FN = 48), excepting Phyllodytes edelmoi and Osteocephalus buckleyi with 2n = 22 (FN = 44) and 2n = 28 (FN = 50), respectively. The NOR location was variable among species and provided valuable phylogenetic information. This marker was located in pair 11 in all species of Trachycephalus, Itapotihyla langsdorffii, and Nyctimantis arapapa, representing the plesiomorphic condition of Lophyohylini. Besides, other apomorphic states were recovered for the clades comprising N. rugiceps and N. siemersi (NOR in pair 5), and Dryaderces pearsoni, Osteocephalus, and Osteopilus (NOR in pair 9). Phyllodytes presented variation for NORs position; they were in pair 2 in P. edelmoi, pair 7 in P. melanomystax, and pair 8 in P. gyrinaethes and P. praeceptor. Polymorphisms in size, number, and activity of this marker were observed for N. siemersi, Osteocephalus fuscifacies, and some species of Trachycephalus. Remarkably, in N. siemersi NORs were detected on a single chromosome in the two specimens studied by this technique, raising the question of how this complex polymorphism is maintained. Interstitial telomeric sequences were found in P. edelmoi, P. melanomystax, and Osteocephalus buckleyi, and their presence seems to be not related to the chromosome reorganization events. Finally, some species showed spontaneous rearrangements, possibly as a consequence of an uncommon phenomenon in anuran cytogenetics: the presence of fragile sites or secondary constrictions not associated with NORs. We propose that this rare feature would have played an important role in the evolution of this group of frogs. From the evidence obtained in this and previous studies, we conclude that Lophyohylini presents a complex chromosome evolution.


Assuntos
Anuros/genética , Cromossomos/genética , Animais , Anuros/classificação , Bandeamento Cromossômico , Sítios Frágeis do Cromossomo/genética , Cromossomos/ultraestrutura , Análise Citogenética , Evolução Molecular , Feminino , Cariótipo , Masculino , Região Organizadora do Nucléolo/genética , Região Organizadora do Nucléolo/ultraestrutura , Filogenia , Polimorfismo Genético , América do Sul , Especificidade da Espécie , Telômero/genética
15.
Am J Surg Pathol ; 44(9): 1235-1243, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32590457

RESUMO

Aggressive natural killer-cell leukemia (ANKL) is a rare, lethal disease with pathologic features that are underdescribed in the literature, particularly in Western nations. In addition, although data on the molecular pathogenesis of ANKL has been reported, evaluation of such data in a clinicopathologic context remains limited. Patients diagnosed with ANKL were identified retrospectively. Detailed demographic and clinicopathologic data were analyzed. We assessed novel markers by immunohistochemistry and performed targeted next-generation sequencing analysis. The study group included 9 men and 3 women with a median age at diagnosis of 47.5 years (range, 20 to 75 y). Two distinct patterns of bone marrow involvement were identified: interstitial and sinusoidal. The neoplastic cells were positive for CD56 and CD94, and negative for surface CD3, CD5, and CD57 in all cases assessed. They were also positive for CD2 (10/12), c-MYC (6/8), BCL2 (6/8), CD16 (5/7), EBER (9/12), CD7 (6/11), pSTAT3 (3/8), CD8 (2/6), PD-L1 (2/8), CD4 (2/11), CD8 (2/6), and CD158 (1/5). Aberrant p53 expression was identified in most (7/8) cases; p53 was strongly expressed in 4 cases. Conventional cytogenetic analysis showed clonal abnormalities in 5 of 12 cases. TP53 mutations were detected in 3 of 6 cases, whereas ASXL1 and TET2 mutations were each detected in 2 of 6 cases. Patients had very poor outcomes despite intensive chemotherapy, with a median survival of 2 months. ANKL exhibits 2 distinct patterns of tissue involvement. Neoplastic cells in ANKL are commonly positive for c-MYC and EBER, and they have a high frequency of p53 overexpression, frequently with corresponding TP53 mutations.


Assuntos
Biomarcadores Tumorais , Leucemia Linfocítica Granular Grande , Adulto , Idoso , Biomarcadores Tumorais/análise , Biomarcadores Tumorais/genética , Análise Citogenética , Análise Mutacional de DNA , Progressão da Doença , Feminino , Predisposição Genética para Doença , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Imuno-Histoquímica , Imunofenotipagem , Leucemia Linfocítica Granular Grande/genética , Leucemia Linfocítica Granular Grande/imunologia , Leucemia Linfocítica Granular Grande/patologia , Leucemia Linfocítica Granular Grande/terapia , Masculino , Pessoa de Meia-Idade , Fenótipo , Estudos Retrospectivos , Fatores de Risco , Resultado do Tratamento , Adulto Jovem
17.
Tunis Med ; 98(2): 168-171, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32395809

RESUMO

BACKGROUND: Mammary analogue secretory carcinoma is a rare new entity of low-grade malignant tumor of salivary glands. It shared the same histologic features and the chromosomal translocation t(12;15)(p13;q25) as secretory carcinoma of the breast. AIM: To highlight the diagnosis approaches and the attitude of management in a case of MASC which is the first case reported in Tunisia. Reported case: A case of MASC of the lower left jugal mucosa was reviewed for its microscopic and immunohistochemical features. Fluorescence in situ hybridization (FISH) for the ETV6-NTRK3 translocation was performed. Surgery was the only treatment required in this case. No signs of local or regional recurrence during the one-year follow-up were noticed. COMMENTARIES: Secretory carcinoma was confused with other salivary gland tumors especially acinic cell carcinoma due to their morphological similarities, making diagnosis dilemma. Fluorescence in-situ hybridization (FISH) is the one definitive finding to confirm the diagnosis of MASC and to differentiate it from the other types of salivary gland tumor. At the present time, no specific therapy is available for patients with MASC.


Assuntos
Carcinoma Secretor Análogo ao Mamário/diagnóstico , Anoctamina-1/análise , Anoctamina-1/metabolismo , Bochecha/patologia , Análise Citogenética , Diagnóstico Diferencial , Feminino , Humanos , Imuno-Histoquímica , Hibridização in Situ Fluorescente , Mamoglobina A/análise , Mamoglobina A/metabolismo , Carcinoma Secretor Análogo ao Mamário/genética , Carcinoma Secretor Análogo ao Mamário/cirurgia , Mucosa Bucal/metabolismo , Mucosa Bucal/patologia , Proteínas de Neoplasias/análise , Proteínas de Neoplasias/metabolismo , Proteínas de Fusão Oncogênica/análise , Proteínas de Fusão Oncogênica/genética , Proteínas S100/análise , Proteínas S100/metabolismo , Tunísia
18.
Georgian Med News ; (300): 124-128, 2020 Mar.
Artigo em Russo | MEDLINE | ID: mdl-32383715

RESUMO

Bayesian approach for the sample size determination (SSD) and a comparison with classical (Frequentist) approach are presented. Credible interval length estimation-type criterion was applied for the Bayesian SSD estimation in population studies of cytogenetic characteristics. The dependence of the sample size (n) on the length of the 95% Credible interval of the population mean has been estimated in the Gaussian approximation of the distribution functions with known variance and an unknown population mean. The Mean and Variance of the prior function in the Bayesian approach were estimated based on published data and the results of our previous studies. Mathematical analysis and graphical visualization of the results was carried out using the software STATISTICA-12, and WinBugs. It is shown that the Bayesian approach achieves an almost two-fold decrease in sample size and provides the possibility of flexible optimization of the planned procedures at the preliminary stage of the study. Further increase inaccuracy of the results is expected due to a more accurate approximation of asymmetric distributions using gamma functions.


Assuntos
Projetos de Pesquisa , Software , Teorema de Bayes , Análise Citogenética , Tamanho da Amostra
19.
Anticancer Res ; 40(5): 2917-2924, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32366443

RESUMO

BACKGROUND/AIM: Acute myeloid leukemia (AML) is a biologically heterogeneous disease that can be classified into de novo AML and secondary AML. Secondary AML can be further divided into therapy-related AML (t-AML) or AML evolving from antecedent hematological disorder (AHD-AML). This study evaluated the characteristics and prognosis of secondary AML in a homogeneous East Asian population who are often under-represented. PATIENTS AND METHODS: This was a retrospective, longitudinal cohort study of Korean AML patients over 18 years old treated between January 2000 and December 2013. A total of 437 de novo AML (80.3%), 41 t-AML (7.5%), and 66 AHD-AML (12.1%) were evaluated. RESULTS: First, we found that secondary AML constituted about 19.7% of all AML cases, and t-AML was more prevalent than AHD-AML. Second, we determined AHD-AML as a prognostic factor for inferior survival, independent of other risk factors (HR=2.137, 95%CI=1.534-2.977, p<0.001). The induction response rates correlated well with the overall survival. Furthermore, AHD-AML was associated with worst treatment outcomes and prognosis regardless of cytogenetic risk or age. Interestingly, t-AML was generally associated with better outcomes compared to AHD-AML despite the similarities in treatment schema. CONCLUSION: Secondary AML represents a broad spectrum of diseases and t-AML should be addressed separately from AHD-AML.


Assuntos
Leucemia Mieloide Aguda/epidemiologia , Adulto , Idoso , Grupo com Ancestrais do Continente Asiático , Estudos de Coortes , Análise Citogenética , Feminino , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Fatores de Risco , Resultado do Tratamento , Adulto Jovem
20.
Hum Genet ; 139(11): 1403-1415, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32451733

RESUMO

Clinically significant copy-number variants (CNVs) known to cause human diseases are routinely detected by chromosomal microarray analysis (CMA). Recently, genome sequencing (GS) has been introduced for CNV analysis; however, sequencing depth (determined by sequencing read-length and read-amount) is a variable parameter across different laboratories. Variating sequencing depths affect the CNV detection resolution and also make it difficult for cross-laboratory referencing or comparison. In this study, by using data from 50 samples with high read-depth GS (30×) and the reported clinically significant CNVs, we first demonstrated the optimal read-amount and the most cost-effective read-length for CNV analysis to be 15 million reads and single-end 50 bp (equivalent to a read-depth of 0.25-fold), respectively. In addition, we showed that CNVs at mosaic levels as low as 30% are readily detected, furthermore, CNVs larger than 2.5 Mb are also detectable at mosaic levels as low as 20%. Herein, by conducting a retrospective back-to-back comparison study of low-pass GS versus routine CMA for 532 prenatal, miscarriage, and postnatal cases, the overall diagnostic yield was 22.4% (119/532) for CMA and 23.1% (123/532) for low-pass GS. Thus, the overall relative improvement of the diagnostic yield by low-pass GS versus CMA was ~ 3.4% (4/119). Identification of cryptic and clinically significant CNVs among prenatal, miscarriage, and postnatal cases demonstrated that CNV detection at higher resolutions is warranted for clinical diagnosis regardless of referral indications. Overall, our study supports low-pass GS as the first-tier genetic test for molecular cytogenetic testing.


Assuntos
Análise Citogenética/métodos , Testes Genéticos/métodos , Genoma Humano/genética , Sequenciamento Completo do Genoma/métodos , Mapeamento Cromossômico/métodos , Variações do Número de Cópias de DNA/genética , Feminino , Feto , Humanos , Masculino , Gravidez , Estudos Retrospectivos
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