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1.
Cytogenet Genome Res ; 160(1): 47-56, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32172236

RESUMEN

The chromosomal constitution of 9 dwarf (D) and 8 semidwarf (SD) lines derived by crossing hexaploid Triticale line NA-75 (AABBRR, 2n = 6x = 42) with Triticumaestivum (AABBDD, 2n = 6x = 42) cv. Chinese Spring was investigated using molecular cytogenetic techniques: fluorescence in situ hybridization and genomic in situ hybridization. A wheat-rye translocation (T4DS.7RL), 8 substitution lines, and a ditelosomic addition line (7RSdt) were identified. In the substitution lines, 1, 2, or 4 pairs of wheat chromosomes, belonging to the A, B, or D genome, were replaced by rye chromosomes. Substitutions between chromosomes belonging to different wheat genomes [5B(5A), 1D(1B)] also occurred. The lines were genetically stable, each carrying 42 chromosomes, except the wheat-rye ditelosomic addition line, which carried 21 pairs of wheat chromosomes and 1 pair of rye telocentric chromosomes (7RS). The chromosome pairing behavior of the lines was studied during metaphase I of meiosis. The chromosome pairing level and the number of ring bivalents were different for each line. Besides rod bivalents, univalent and multivalent associations (tri- and quadrivalents) were also detected. The main goal of the experiment was to develop genetically stable wheat/Triticale recombinant lines carrying chromosomes/chromatin fragments originating from the R genome of Triticale line NA-75. Introgression of rye genes into hexaploid wheat can broaden its genetic diversity, and the newly developed lines can be used in wheat breeding programs.


Asunto(s)
Meiosis/genética , Triticale/genética , Triticum/genética , Cromatina/metabolismo , Emparejamiento Cromosómico , Cromosomas de las Plantas , Cruzamientos Genéticos , Análisis Citogenético , Genes de Plantas , Variación Genética , Hibridación in Situ , Hibridación Fluorescente in Situ , Metafase , Ploidias , Secale/genética , Especificidad de la Especie , Translocación Genética
4.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 28(1): 136-140, 2020 Feb.
Artículo en Chino | MEDLINE | ID: mdl-32027266

RESUMEN

OBJECTIVE: To analyze the relationship between cytogenetic changes and the progression in the patients with chronic myeloid leukemia (CML) during the treatment with tyrosine kinase inhibitor (TKI). METHODS: The chromosome G banding of 150 patients with CML treated in our hospital, was carried out to analyze the karyotype by the 24 h short-term culture or direct method of bone marrow cells, and the point mutation of the ABL kinase area was detected, the relationship between cytogenetic changes and the evolution of the disease course was analyzed. RESULTS: The indirect fluorescence in situ hybridization showed that the BCR-ABL fusion gene of 150 patients was positive, out of which 142 cases showed positive Philadelphia (Ph) (94.67%), 8 cases with Ph negative (5.33%). Among 142 cases with Ph positive on the first diagnosis, and 14 cases (9.86%) with additional chromosome abnormality (9.86%), 4 cases (2.82%) with mutation translocation with 124 cases (87.32%), standard translocation t (9; 22) (q34; Q11) were found. Out of the 14 patients with additional chromosomal abnormalities, 8 cases with "main pathmay" abnormalities, 2 case with -Y abnormalities, and 4 cases with "secondary pathway" abnormalities were observed. During TKI treatment, additional chromosomal abnormalities were found in 46 patients with standard translocation and abnormal number of chromosomes, and the incidence of disease progression and point mutation were higher (P<0.05). Compared with patients with the standard translocation, the disease-free survival rate of the patients diagnosed as CML at 1st visit and with additional chromosome abnormality was significantly decreased (P<0.05), but the overall survival rate showed no significantly different (P>0.05). Compared with patients without additional cvtogenetic aberrations, the disease free and overall survival rate of the patients with additional cytogenetic aberrations during the TKI treatment of CML in chronic phase were significantly decreased (P<0.05). CONCLUSION: Some CML patients may have additional chromosomal abnormalities during the onset and development of the disease, and these patients are at higher risk of disease progression.


Asunto(s)
Leucemia Mielógena Crónica BCR-ABL Positiva , Cromosoma Filadelfia , Inhibidores de Proteínas Quinasas/uso terapéutico , Aberraciones Cromosómicas , Análisis Citogenético , Citogenética , Humanos , Hibridación Fluorescente in Situ , Leucemia Mielógena Crónica BCR-ABL Positiva/tratamiento farmacológico , Translocación Genética
5.
Zhonghua Xue Ye Xue Za Zhi ; 41(1): 10-15, 2020 Jan 14.
Artículo en Chino | MEDLINE | ID: mdl-32023748

RESUMEN

Objective: To analyze the frequency and composition of risk-related cytogenetic abnormalities (CAs) in patients with newly-diagnosed multiple myeloma (NDMM) . Methods: The frequency and composition of risk-related CAs from a cohort of 1 015 Chinese patients with NDMM were determined by interphase fluorescence in situ hybridization (iFISH) , individually or in combination. Results: Of the cohort of 1 015 Chinese patients with NDMM, the frequencies of IgH arrangement, del (13q) /13q14, 1q gain and del (17p) were 54.0%, 46.4%, 46.1% (35.8% and 12. 7% for 3 or more than 3 copies) and 9.9%, respectively. Among 454 patients who had the baseline information for all risk-related CAs [except t (14;20) , which was not covered by the FISH panels performed routinely at all five centers], the frequencies of t (4;14) , t (11;14) or t (14;20) were 14.1%, 11.2% and 4.8%, respectively; of them, 44.3% patients carried 2 or more CAs (28.0%, 13.4% and 2.9% for 2, 3 or ≥4 CAs) ; 83.3%, 95.0% or 68.6% patients with 1q gain, del (17p) or IgH rearrangement had 1 or more additional CA (s) , with del (13q) /13q14 as the most frequently accompanied CA; 57.7% patients carried at least 1 HRCA; the incidences of double-hit (DH) MM (DHMM) (=2 HRCAs) and triple-hit (TH) (THMM) (≥3 HRCAs) were 14.3% and 2.9%, respectively. Conclusions: Our results provided an up-to-date profile of CAs in Chinese NDMM patients, which revealed that approximately 58% patients might carry at least 1 HRCA, and 17% could experience so-called DHMM or THMM who presumably had the worst outcome.


Asunto(s)
Mieloma Múltiple , Aberraciones Cromosómicas , Análisis Citogenético , Humanos , Hibridación Fluorescente in Situ , Pronóstico , Estudios Retrospectivos
6.
Medicine (Baltimore) ; 99(3): e18888, 2020 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-32011516

RESUMEN

RATIONALE: The success of tyrosine kinase inhibitor (TKI) therapy has greatly prolonged the survival time of patients with chronic myeloid leukemia (CML), harboring the characteristic Philadelphia (Ph) chromosome. However, a fraction of patients, achieving complete cytogenetic response after TKI therapy, develop a myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML) with additional clonal chromosomal abnormalities in Philadelphia-negative cells (CCA/Ph-). PATIENT CONCERNS: A 56-year-old woman with AML, developing from Philadelphia-negative CML after TKI therapy. She showed 6 kinds of somatic variants-CEBPA, ATRX, WT1, CSMD1, IKZF1, and LRP1B mutation after diagnosed as AML. DIAGNOSIS: The patient was diagnosed with chronic phase CML that developed to AML after achieving durable complete cytogenetic response (CCR) and major molecular response (MMR). INTERVENTIONS: The patient was treated with TKI therapy at the period of CML. When diagnosed with AML, she received induction chemotherapy regimens, consolidation therapy, and allogeneic hematopoietic stem cell transplantation subsequently. OUTCOMES: The patient has been CCR and MMR for nearly 4 years, and has achieved complete remission after intervention related to AML. She is now preparing for allogeneic hematopoietic stem cell transplantation. LESSONS: These rare occurrences highlight the importance of exploring the relevant pathogenesis of AML developing from CML after TKI therapy. In addition to monitoring molecular changes in the course of CML, cytogenetic analysis, or next-generation sequencing of CML patients should be performed.


Asunto(s)
Leucemia Mielógena Crónica BCR-ABL Positiva/complicaciones , Leucemia Mieloide Aguda/etiología , Antineoplásicos/uso terapéutico , Cromosomas Humanos Par 1 , Cromosomas Humanos Par 19 , Análisis Citogenético , Femenino , Humanos , Leucemia Mielógena Crónica BCR-ABL Positiva/tratamiento farmacológico , Leucemia Mielógena Crónica BCR-ABL Positiva/genética , Leucemia Mieloide Aguda/tratamiento farmacológico , Leucemia Mieloide Aguda/genética , Persona de Mediana Edad , Mutación , Inhibidores de Proteínas Quinasas/uso terapéutico , Translocación Genética
7.
Cytogenet Genome Res ; 160(2): 94-99, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32062647

RESUMEN

In this study, we analyzed the karyotype of Salvator merianae (Teiidae) from the Brazilian semiarid region using different cytogenetic markers. Chromosomes were examined by classical (Giemsa and AgNOR staining) and molecular (FISH with ribosomal, telomeric, and microsatellite probes) cytogenetic approaches. S. merianae showed a diploid chromosome number of 2n = 38 (10 biarmed macrochromosomes + 28 microchromosomes). No sex-linked chromosome heteromorphisms were observed. Clusters of 18S/28S rDNA were localized in the terminal region of the long arm of pair 2. In addition to the typical telomeric signals, (TTAGGG)n repeats were detected in the pericentromeric region of some macrochromosome pairs, which might indicate the occurrence of chromosomal rearrangements via chromosome fusions. Hybridization signals of the microsatellite probes (GA)n, (GAA)n, and (GAG)n were uniformly distributed across all chromosomes, while (CA)n, (CAA)n, and (CAC)n produced brighter signals in the telomeric and pericentromeric regions of specific chromosome pairs. The comparison with previous studies demonstrates that, despite the wide distribution of S. merianae, the macrostructure organization of the karyotype remained unchanged, showing stability in diploid number and chromosome morphology.


Asunto(s)
Análisis Citogenético/veterinaria , Cariotipificación/veterinaria , Lagartos/genética , Animales , Cromosomas/genética , Diploidia , Evolución Molecular , Femenino , Cariotipo , Masculino
9.
Einstein (Sao Paulo) ; 18: eAO4966, 2020.
Artículo en Inglés, Portugués | MEDLINE | ID: mdl-31994605

RESUMEN

OBJECTIVE: To validate multilineage score system correlating results of flow cytometry, cytogenetics, cytomorphology and histology from samples of patients with suspected myelodysplastic syndrome or cytopenia of unknown origin. METHODS: A retrospective study analyzing laboratory data of 49 patients with suspected myelodysplastic syndrome or cytopenia of unknown origin, carried out between May and September 2017. The inclusion criteria were availability of flow cytometry results, and at least one more method, such as morphology, histology or cytogenetics. Thirty-eight patients were classified as diagnosis of myelodysplastic syndromes, whereas 11 were classified as normal. Patients were evaluated based on score systems, Ogata score and flow cytometry multilineage score. RESULTS: Comparing the scores obtained in the Ogata score and the multilineage score, it was observed that in four cases the Ogata score was zero or 1 point, while the multilineage score was higher than 3 points. In addition, in 12 cases with Ogata score of 2, the multilineage score was greater than 3. CONCLUSION: The flow cytometry multilineage score system demonstrated to be more effective in dysplasia analysis, by assessing the erythroid, monocytic, granulocytic and precursor cell lineages, apart from the parameters evaluated by the Ogata score.


Asunto(s)
Citometría de Flujo/normas , Síndromes Mielodisplásicos/patología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Biopsia , Células de la Médula Ósea/patología , Niño , Preescolar , Análisis Citogenético/métodos , Análisis Citogenético/normas , Células Eritroides/patología , Femenino , Citometría de Flujo/métodos , Granulocitos/patología , Humanos , Lactante , Masculino , Persona de Mediana Edad , Monocitos/patología , Estándares de Referencia , Reproducibilidad de los Resultados , Estudios Retrospectivos , Adulto Joven
10.
PLoS One ; 15(1): e0227117, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-31923267

RESUMEN

Hypospadias, disorder of sex development (DSD), is a sporadic congenital abnormality of the genital region in male ruminants, which is characterized by a non-fused urethra during fetal development. Detailed clinical examination classified the hypospadias phenotype of a male Holstein calf studied here as the perineal type. In combined use of cytogenetic analysis and whole genome sequencing, a non-mosaic, pseudo-monosomy 59, XY + tan(18;27) was detected. This chromosomal aberration had its origin in a tandem fusion translocation of the bovine autosomes (BTA) 18 and 27 with an accompanying loss of genomic sequences mainly in the distal end of BTA 18 and the proximal end of BTA 27. The resulting phenotype included hypospadias, growth retardation and ventricular septal defect.


Asunto(s)
Enfermedades de los Bovinos/genética , Aberraciones Cromosómicas , Defectos del Tabique Interventricular/genética , Hipospadias/genética , Translocación Genética/genética , Animales , Bovinos , Análisis Citogenético/métodos , Defectos del Tabique Interventricular/veterinaria , Hipospadias/veterinaria , Masculino , Monosomía/genética , Secuenciación Completa del Genoma/métodos
11.
PLoS One ; 14(12): e0226552, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-31869360

RESUMEN

BACKGROUND: Imatinib mesylate (IM) is a first-line treatment option for patients with chronic myeloid leukemia (CML). Patients who fail or are intolerant to IM therapy are treated with more expensive second and third-generation tyrosine kinase inhibitors. Patients show wide variation in trough concentrations in response to standard dosing. Thus, many patients receive subtherapeutic or supratherapeutic doses. Therapeutic drug monitoring (TDM) may improve dose management that, in turn, may reduce costs and improve outcomes. However, TDM also adds to the cost of patient care. The objective of this study was to determine the cost-effectiveness of TDM for generic IM therapy. METHODS: We developed a microsimulation model for the trough plasma concentration of IM which is related to a cytogenetic or molecular response. We compared two cohorts: one with TDM and one without TDM (NTDM). The lifetime incremental cost-effectiveness ratio (ICER) was calculated using quality-adjusted life years (QALYs) as the effectiveness measure. One-way and probabilistic sensitivity analyses were performed. RESULTS: The lifetime cost and QALY of treatment with TDM were $2,137K [95% Ci: 2,079K; 2,174K] and 12.37 [95% CI: 12.07; 12.55], respectively. The cost and QALY of NTDM were $2,132K [95% CI: 2,091K; 2,197K] and 12.23 [95% CI: 11.96; 12.50], respectively. The incremental cost and QALY for TDM relative to NTDM was $4,417 [95% CI: -52,582; 32,097]) and 0.15 [95% CI: -0.13; 0.28]. The ICER for TDM relative to NTDM was $30,450/QALY. Probabilistic sensitivity analysis showed that TDM was cost-effective relative to NTDM in 90% of the tested scenarios at a willingness-to-pay threshold of $100,000/QALY. CONCLUSIONS: Although the impact of TDM is modest, the cost-effectiveness over a lifetime horizon (societal perspective, ($30,450/QALY) falls within the acceptable range (< $100k/QALY).


Asunto(s)
Monitoreo de Drogas/economía , Mesilato de Imatinib/uso terapéutico , Leucemia Mielógena Crónica BCR-ABL Positiva/tratamiento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/economía , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Simulación por Computador , Análisis Costo-Beneficio , Análisis Citogenético , Monitoreo de Drogas/métodos , Resistencia a Antineoplásicos/genética , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos/economía , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos/epidemiología , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos/genética , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos/terapia , Medicamentos Genéricos/economía , Medicamentos Genéricos/uso terapéutico , Trasplante de Células Madre Hematopoyéticas/economía , Trasplante de Células Madre Hematopoyéticas/estadística & datos numéricos , Humanos , Mesilato de Imatinib/economía , Leucemia Mielógena Crónica BCR-ABL Positiva/economía , Leucemia Mielógena Crónica BCR-ABL Positiva/epidemiología , Leucemia Mielógena Crónica BCR-ABL Positiva/genética , Cumplimiento de la Medicación/estadística & datos numéricos , Pruebas de Farmacogenómica , Años de Vida Ajustados por Calidad de Vida , Análisis de Supervivencia
12.
Cytogenet Genome Res ; 159(3): 151-161, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-31683269

RESUMEN

Trachymyrmex is one of the most species-rich genera within fungus-farming ants and presents intraspecific cytogenetic polymorphisms as well as possible cryptic species. This ant genus is currently paraphyletic. Therefore, to unravel systematic and taxonomic misunderstandings, it is necessary to incorporate new information. We aimed to cytogenetically and genetically examine Trachymyrmex holmgreni populations from southern and northern Brazil to identify intraspecific chromosomal variations that support incipient speciation and reveal the species' position in a molecular phylogeny. Our cytogenetic approach did not show population variation in the mapping of both 18S rDNA and the TTAGG(6) motif, presenting instead a pattern characteristic of correlated species. However, the clustered pattern of the microsatellite GA(15) showed significant differences among populations: a well-defined block in each homologue, distinctly irregular signs between homologues, and blocks in 2 pairs of homologues. Our phylogenetic reconstruction yielded unexpected results, grouping representatives of 3 former morphological groups into 1 clade, namely T. urichii, T. papulatus, and T. holmgreni. Previously, it was suggested that northern and southern populations of T. holmgreni may be undergoing incipient speciation, but we can only indicate that the southernmost population differs prominently from the others in its distribution pattern of the microsatellite GA(15). Our study also supports the uniformity of karyotypes and repetitive DNA from both telomeric sequences and ribosomal DNA in Trachymyrmex studied here. In addition, we clarify some phylogenetic uncertainties within the genus and suggest further relevant systematic changes. Finally, additional studies utilizing other probes and additional populations may allow the detection of hidden genetic variation.


Asunto(s)
Hormigas/genética , Bandeo Cromosómico , Análisis Citogenético , Hongos/fisiología , Filogenia , Animales , Hormigas/clasificación , Hormigas/fisiología , Conducta Animal , Femenino , Masculino
13.
Cytogenet Genome Res ; 159(2): 81-87, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-31614359

RESUMEN

Lipoblastoma is a rare benign neoplasm with overlapping histology with other lipomatous tumors. Genetic aberrations including translocations of 8q and splitting of the PLAG1 probe leading to "promoter swapping" and gains of chromosome 8 or PLAG1 foci have been described in lipoblastoma. Here, we report 3 lipoblastomas revealing novel genetic aberrations involving PLAG1: a high level of PLAG1 amplification up to 50 copies in a 4-year-old girl with recurrence of a right flank mass, a partial deletion of PLAG1 with the flanking junction breakpoints involving the 3'PLAG1 and 5'HAS2 genes in a 17-month-old boy with a retroperitoneal mass, and an insertion of 2q31 into 8q11.2 and translocation of 8q to 2q with the latter translocated onto 12q leading to separation of the PLAG1 FISH probe in a 5-year-old girl with a left back mass. Our novel cytogenetic findings further expand the mechanisms of PLAG1 transcriptional upregulation in lipoblastoma pathogenesis.


Asunto(s)
Proteínas de Unión al ADN/genética , Lipoblastoma/genética , Preescolar , Aberraciones Cromosómicas , Cromosomas Humanos Par 8/genética , Análisis Citogenético/métodos , Femenino , Humanos , Lactante , Masculino , Translocación Genética/genética
14.
J Insect Sci ; 19(5)2019 Sep 01.
Artículo en Inglés | MEDLINE | ID: mdl-31587063

RESUMEN

In this study, chromosomal characteristics of Eratigena agrestris (Agelenidae) were investigated for the first time. Karyotype features including diploid chromosome number, sex chromosome system, chromosome morphology, and meiotic behavior were obtained from specimens collected in two localities of Mediterranean region. A spreading method including dissection, hypotonization, fixation, and staining was used to prepare the chromosome slides. In a total, 10 adult males were used due to having high numbers of dividing cells. Cytogenetical results showed that the diploid chromosome number and sex chromosome system was 2n♂ = 42 (X1X20). The sex chromosomes were identified tentatively. All chromosomes were telocentric. Relative chromosome lengths of autosomal pairs ranged between 5.65 and 3.32%, and relative chromosome lengths of X1 and X2 were 5.33 and 4.19%, respectively. In the first meiotic division stages, bivalents usually had one chiasma, but some had two chiasmata. At the end of the meiosis, two kinds of nuclei, with or without sex chromosomes, have occurred. These results contribute to a better characterization of the Agelenidae cytogenetic.


Asunto(s)
Análisis Citogenético , Arañas/genética , Animales , Femenino , Cariotipo , Masculino , Cromosomas Sexuales , Turquia
16.
Zhonghua Xue Ye Xue Za Zhi ; 40(8): 644-649, 2019 Aug 14.
Artículo en Chino | MEDLINE | ID: mdl-31495130

RESUMEN

Objectives: To evaluate the clinical characteristics and prognosis of high risk cytogenetic abnormalities (HRCA) and various combinations of cytogenetic abnormality in patients with newly-diagnosed multiple myeloma (NDMM) . Methods: This retrospective study collected 182 NDMM patients in the First Affiliated Hospital of Jilin University between Nov. 2009 and May 2018. HRCA included 1q+, del (17p) , t (4;14) , and t (14;16) detected by FISH, and non-HRCA included del (13q) , t (11;14) detected by FISH. The clinical characteristics among three groups, including cases who carrying a single HRCA, 1 HRCA in combination with non-HRCA and cases carrying two or more HRCAs (double/triple-hit) were observed. Kaplan-Meier curve was used to analyze both progression-free survival (PFS) and overall survival (OS) for the three groups. Results: The survivals of patients with 1 HRCA in combination with non-HRCA were similar to those with two or more HRCAs (double/triple-hit) , the median PFS (mPFS) was 19.1 m vs 12.1 m (P=0.248) and median OS (mOS) was 29.6 m vs 29.3 m (P=0.774) . Furthermore, the prognosis of these two groups were both inferior to patients with a single HRCA, respectively. (mPFS: 32.2 m, P=0.040, P=0.001; mOS: 42.3 m, P=0.021, P=0.041) . Strikingly, both the mPFS and the mOS of patients with 1 HRCA in combination with non-HRCA (regardless of high risk or not) were significantly shorter than that of cases with a single HRCA (mPFS: 15.1 m vs 32.2 m, HR=2.126, 95%CI 1.176-3.843, P=0.005; mOS: 29.3 m vs 42.3 m, HR=1.442, 95%CI 0.705-2.950, P=0.011) . Conclusion: It is of prognostic significance value for detecting double/triple-hit based on FISH cytogenetics in NDMM.


Asunto(s)
Trastornos de los Cromosomas , Mieloma Múltiple , Aberraciones Cromosómicas , Análisis Citogenético , Humanos , Pronóstico , Estudios Retrospectivos
17.
Int J Radiat Biol ; 95(12): 1659-1667, 2019 12.
Artículo en Inglés | MEDLINE | ID: mdl-31490087

RESUMEN

Purpose: This paper describes how the BioDoseNet image repository was used as a training tool for the dicentric assay.Materials and methods: The training was implemented in three phases: introduction to dicentric scoring, dose response curve elaboration and dose assessment exercise. Four labs without previous experience in the dicentric assay participated and four modules of the repository were used.Results: The labs become familiar with aberrations induced by ionizing radiation. The labs were able to generate data for the elaboration of a dose response curve and then successfully estimated doses and irradiated fractions in six blind samples.Conclusions: The performance of these laboratories during the exercise demonstrates the efficacy of the BioDoseNet image repository as a training tool and the utility of web based scoring for the dicentric assay community.


Asunto(s)
Aberraciones Cromosómicas/efectos de la radiación , Análisis Citogenético , Bases de Datos Factuales , Imagen Molecular , Calibración , Relación Dosis-Respuesta en la Radiación , Metafase/genética , Metafase/efectos de la radiación
18.
BMC Cancer ; 19(1): 913, 2019 Sep 13.
Artículo en Inglés | MEDLINE | ID: mdl-31514735

RESUMEN

BACKGROUND: Gastrointestinal stromal tumor (GIST) is the most common primary mesenchymal neoplasm of the gastrointestinal tract. Mutations of KIT and platelet-derived growth factor receptor alpha have been well characterized in GISTs. Patients with KIT mutations are generally sensitive to treatment with tyrosine kinase inhibitors. However, some patients with GIST, while initially sensitive to TKIs, gain resistance in later stages of treatment. Heterologous rhabdomyomsarcomatous dedifferentiation of advanced GISTs after long-term imatinib mesylate (IM) therapy has been reported. In these cases, the underlying molecular mechanism of tumor progression and transformation is unclear. CASE PRESENTATION: We report one such patient with rhabdomyosarcomatous dedifferentiation of a GIST without metastatic disease after brief 3-month therapy with IM. The tumor was composed of two distinct phenotypes, a CD117 negative region with rhabdomyosarcomatous differentiation directly adjacent to a CD117 positive classic GIST region. Molecular analysis identified the activating KIT exon 11 mutation in both regions, indicating a common origin for both phenotypes. Additionally, the dedifferentiated component contained two synonymous variants in platelet-derived growth factor receptor alpha and KIT. The increased number of synonymous variants in the rhabdomyosarcomatous region may reflect increased genetic instability of this tumor that may have resulted in the loss of CD117 expression in the dedifferentiated component. CONCLUSION: This study adds to the growing consensus that rhabdomyosarcomatous GIST progresses from a common GIST primary tumor. The role of IM in this progression is uncertain; however short duration of IM treatment in this study supports the hypothesis that rhabdomyosarcomatous GIST progression is not a consequence of IM therapy. Furthermore, we provide additional information supporting the observation that CD117 negative rhabdomyosarcomatous transformation maintains the activating KIT variant without KIT expression.


Asunto(s)
Transformación Celular Neoplásica , Tumores del Estroma Gastrointestinal/diagnóstico , Rabdomiosarcoma/patología , Anciano , Transformación Celular Neoplásica/genética , Análisis Citogenético , Tumores del Estroma Gastrointestinal/genética , Secuenciación de Nucleótidos de Alto Rendimiento , Humanos , Inmunohistoquímica , Masculino , Mutación , Proteínas Proto-Oncogénicas c-kit/genética , Rabdomiosarcoma/diagnóstico por imagen , Rabdomiosarcoma/genética , Tomografía Computarizada por Rayos X
19.
J Genet ; 982019 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-31544782

RESUMEN

Although it is known that the parental carriers of chromosomal translocation are considered to be at high risk for spontaneous abortion and embryonic death, normal gestation and delivery remain possible. This study aims to investigate the genetic factors of a Chinese infant with multiple malformations and severe postnatal development retardation. In this study, the routine cytogenetic analysis, chromosomal microarray analysis (CMA) and fluorescence in situ hybridization (FISH) analysis were performed. Conventional karyotype analyses revealed normal karyotypes of all family members. CMA of the DNA of the proband revealed a 8.3 Mb duplication of 5q35.1-qter and a 6.9 Mb deletion of 11q24.3-qter. FISH analyses verified a paternal tiny translocation between the long arm of chromosomes 5 and 11. Our investigation serves to provide important information on genetic counselling for the patient and future pregnancies in this family. Moreover, the combined use of CMA and FISH is effective for clarifying pathogenically submicroscopic copy number variants.


Asunto(s)
Cromosomas Humanos Par 11 , Cromosomas Humanos Par 5/genética , Discapacidades del Desarrollo/genética , Discapacidad Intelectual/genética , Translocación Genética , Anomalías Múltiples/genética , Deleción Cromosómica , Duplicación Cromosómica/genética , Análisis Citogenético , Humanos , Hibridación Fluorescente in Situ , Lactante , Cariotipificación , Masculino , Análisis por Micromatrices , Trisomía/genética , Trisomía/patología
20.
Blood ; 134(21): 1821-1831, 2019 11 21.
Artículo en Inglés | MEDLINE | ID: mdl-31527074

RESUMEN

B-cell prolymphocytic leukemia (B-PLL) is a rare hematological disorder whose underlying oncogenic mechanisms are poorly understood. Our cytogenetic and molecular assessments of 34 patients with B-PLL revealed several disease-specific features and potential therapeutic targets. The karyotype was complex (≥3 abnormalities) in 73% of the patients and highly complex (≥5 abnormalities) in 45%. The most frequent chromosomal aberrations were translocations involving MYC [t(MYC)] (62%), deletion (del)17p (38%), trisomy (tri)18 (30%), del13q (29%), tri3 (24%), tri12 (24%), and del8p (23%). Twenty-six (76%) of the 34 patients exhibited an MYC aberration, resulting from mutually exclusive translocations or gains. Whole-exome sequencing revealed frequent mutations in TP53, MYD88, BCOR, MYC, SF3B1, SETD2, CHD2, CXCR4, and BCLAF1. The majority of B-PLL used the IGHV3 or IGHV4 subgroups (89%) and displayed significantly mutated IGHV genes (79%). We identified 3 distinct cytogenetic risk groups: low risk (no MYC aberration), intermediate risk (MYC aberration but no del17p), and high risk (MYC aberration and del17p) (P = .0006). In vitro drug response profiling revealed that the combination of a B-cell receptor or BCL2 inhibitor with OTX015 (a bromodomain and extra-terminal motif inhibitor targeting MYC) was associated with significantly lower viability of B-PLL cells harboring a t(MYC). We concluded that cytogenetic analysis is a useful diagnostic and prognostic tool in B-PLL. Targeting MYC may be a useful treatment option in this disease.


Asunto(s)
Leucemia Prolinfocítica Tipo Células B/genética , Proteínas Proto-Oncogénicas c-myc/genética , Proteína p53 Supresora de Tumor/genética , Anciano , Anciano de 80 o más Años , Aberraciones Cromosómicas , Análisis Citogenético , Femenino , Humanos , Masculino , Persona de Mediana Edad , Pronóstico
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