RESUMO
Chromosomal aberrations of T-cell receptor (TCR) gene loci often involve the TCRalphadelta (14q11) locus and affect various known T-cell oncogenes. A systematic fluorescent in situ hybridization (FISH) screening for the detection of chromosomal aberrations involving the TCR loci, TCRalphadelta (14q11), TCRbeta (7q34) and TCRgamma (7p14), has not been conducted so far. Therefore, we initiated a screening of 126 T-cell acute lymphoblastic leukemia (T-ALL) and T-cell lymphoblastic lymphoma cases and 19 T-ALL cell lines using FISH break-apart assays for the different TCR loci. Genomic rearrangements of the TCRbeta locus were detected in 24/126 cases (19%), most of which (58.3%) were not detected upon banding analysis. Breakpoints in the TCRalphadelta locus were detected in 22/126 cases (17.4%), whereas standard cytogenetics only detected 14 of these 22 cases. Cryptic TCRalphadelta/TCRbeta chromosome aberrations were thus observed in 22 of 126 cases (17.4%). Some of these chromosome aberrations target new putative T-cell oncogenes at chromosome 11q24, 20p12 and 6q22. Five patients and one cell line carried chromosomal rearrangements affecting both TCRbeta and TCRalphadelta loci. In conclusion, this study presents the first inventory of chromosomal rearrangements of TCR loci in T-ALL, revealing an unexpected high number of cryptic chromosomal rearrangements of the TCRbeta locus and further broadening the spectrum of genes putatively implicated in T-cell oncogenesis.
Assuntos
Rearranjo Gênico do Linfócito T/genética , Genes Codificadores da Cadeia beta de Receptores de Linfócitos T/genética , Leucemia-Linfoma de Células T do Adulto/epidemiologia , Leucemia-Linfoma de Células T do Adulto/genética , Adolescente , Adulto , Criança , Pré-Escolar , Feminino , Genes Codificadores da Cadeia alfa de Receptores de Linfócitos T/genética , Genes Codificadores da Cadeia delta de Receptores de Linfócitos T/genética , Humanos , Hibridização in Situ Fluorescente , Incidência , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Translocação GenéticaRESUMO
To accurately estimate the incidence of HOX11L2 expression, and determine the associated cytogenetic features, in T-cell acute lymphoblastic leukemia (T-ALL), the Groupe Français de Cytogénétique Hématologique (GFCH) carried out a retrospective study of both childhood and adult patients. In total, 364 patients were included (211 children =15 years and 153 adults), and 67 (18.5%) [47 children (22.4%) and 20 adults (13.1%)] were shown to either harbor the t(5;14)q35;q32) translocation or express the HOX11L2 gene or both. Most of the common hematological parameters did not show significant differences within positive and negative populations, whereas the incidence of CD1a+/CD10+ and cytoplasmic CD3+ patients was significantly higher in positive than in negative children. Out of the 63 positive patients investigated by conventional cytogenetics, 32 exhibited normal karyotype, whereas the others 31 showed clonal chromosome abnormalities, which did not include classical T-ALL specific translocations. Involvement of the RANBP17/HOX11L2 locus was ascertained by fluorescence in situ hybridization in six variant or alternative (three-way translocation or cytogenetic partner other than 14q32) translocations out of the 223 patients. Our results also show that HOX11L2 expression essentially occurs as a result of a 5q35 rearrangement, but is not associated with another identified T-ALL specific recurrent genetic abnormality, such as SIL-TAL fusion or HOX11 expression.
Assuntos
Cromossomos Humanos Par 14/genética , Cromossomos Humanos Par 5/genética , Proteínas de Homeodomínio/genética , Leucemia-Linfoma de Células T do Adulto/genética , Proteínas Oncogênicas/genética , Translocação Genética , Adolescente , Adulto , Criança , Pré-Escolar , Aberrações Cromossômicas , Células Clonais , Feminino , Humanos , Imunofenotipagem , Hibridização in Situ Fluorescente , Cariotipagem , Masculino , Ploidias , Proteínas Proto-Oncogênicas , Estudos Retrospectivos , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Taxa de SobrevidaRESUMO
In South Belgium (Wallonia), the 'triple test' was introduced in 1990-1991, and is nowadays a widely accepted screening method for assessment of trisomy 21 risk in pregnancy. The 'triple test' is not regulated and can be freely performed by any biomedical lab, making epidemiological data unavailable. By contrast, cytogenetic investigations are limited to a few genetic centres, and accurate statistics can be easily built from their files. During the period 1984-1989, a total of 244 trisomy 21 (1/876 pregnancies) were diagnosed in the Genetic Centres of Liège and Loverval, 42 (17%) of them prenatally. During the period 1993-1998, 294 trisomy 21 (1/704 pregnancies) were observed, 165 (56%) of which prenatally, and more than 90% of affected pregnancies were terminated. Even after correction for late foetal loss of trisomic foetuses, the difference is highly significant, and corresponds to a theoretical shift in the incidence of trisomy 21 at birth from 1/794 to 1/1606. As no remarkable progress occurred in other non-invasive prenatal screening procedures or general health care policies in Belgium, the most reasonable explanation is the use on a large scale of triple test by pregnant women, and the election of termination for most affected pregnancies.
Assuntos
Síndrome de Down/diagnóstico , Adulto , Bélgica/epidemiologia , Síndrome de Down/epidemiologia , Feminino , Humanos , Incidência , Recém-Nascido , Programas de Rastreamento/métodos , Idade Materna , Gravidez , Gravidez de Alto Risco , Diagnóstico Pré-Natal/métodos , Estatística como AssuntoRESUMO
We present four children from two families with the typical 11q- phenotype resulting from an unbalanced segregation of a parental translocation. In the first family, the father had a 46,XY,t(5;11)(q24;q23.3) constitution. The father of the three other children had a 46,XY,t(11;17)(q23;p13) translocation. Despite associated partial deletion, three of the children had a typical 11q- phenotype. The fourth one, whose pregnancy was terminated in the second trimester, had a hypoplastic left heart but no other considered gross anomalies. A review of 36 previous cases, including 5 due to translocations (4 familial rearrangements, and 1 of unknown origin) is given with emphasis on the relationships between break-points and phenotype. Undescribed manifestations in our patients include agenesis of corpus callosum adactyly and malrotation of the gut.
Assuntos
Anormalidades Múltiplas/genética , Aberrações Cromossômicas/genética , Deleção Cromossômica , Cromossomos Humanos Par 11 , Doenças Fetais/genética , Anormalidades Múltiplas/embriologia , Encéfalo/anormalidades , Aberrações Cromossômicas/embriologia , Aberrações Cromossômicas/patologia , Transtornos Cromossômicos , Cromossomos Humanos Par 11/ultraestrutura , Feminino , Morte Fetal/genética , Cardiopatias Congênitas/genética , Humanos , Recém-Nascido , Masculino , Translocação GenéticaRESUMO
In 1990, Lambotte syndrome was reported as an apparently autosomal recessive multiple congenital anomaly/mental retardation (MCA/MR) syndrome observed in 4 of 12 sibs from a probably consanguineous mating [Verloes et al., Am J Med Genet 1990; 37:119-123]. Major manifestations included intrauterine growth retardation (IUGR), microcephaly, large soft pinnae, hypertelorism, beaked nose, and extremely severe neurologic impairment, with holoprosencephaly in one instance. After the observation of a further affected child born of one unaffected sister, in situ hybridization analysis and chromosome painting techniques demonstrated a subtle t(2;4)(q37.1; p16.2) translocation in the mother, suggesting a combination of 2q/4p trisomy/monosomy in all of the affected children of the family. Many private sporadic or recurrent MCA/MR syndromes maybe due to similar symmetric translocations, undetectable by conventional banding techniques.
Assuntos
Aberrações Cromossômicas/genética , Anormalidades Craniofaciais/genética , Deficiência Intelectual/genética , Translocação Genética/genética , Anormalidades Múltiplas/genética , Transtornos Cromossômicos , Cromossomos Humanos Par 2/genética , Cromossomos Humanos Par 4/genética , Feminino , Transtornos do Crescimento/genética , Humanos , Recém-Nascido , Cariotipagem , Gravidez , SíndromeRESUMO
We investigate the feasibility of CD34-selected peripheral blood stem cell (PBSC) transplantation followed by pre-emptive CD8-depleted donor lymphocyte infusions (DLI) after a minimal conditioning regimen. Six patients with advanced hematological malignancies ineligible for a conventional myeloablative transplant (n=5) or metastatic renal cell carcinoma (n=1), and with an HLA-identical (n=4) or alternative (n=2) donor were included. The nonmyeloablative conditioning regimen consisted in 2 Gy TBI alone (n=4), 2 Gy TBI and fludarabine (RCC patient, n=1) or cyclophosphamide and fludarabine (patient who had previously received 12 Gy TBI, n=1). Post transplant immunosuppression was carried out with cyclosporin (CyA) and mycophenolate mofetil (MMF). Initial engraftment was achieved in all patients. One out of six patients (17%) experienced grade > or =2 acute GVHD only after abrupt cyclosporin discontinuation and alpha interferon therapy for life-threatening tumor progression. T-cell chimerism was 23% (19-30) on day 28, 32% (10-35) on day 100, 78% (49-95) on day 180 and 99.5% (99-100) on day 365. Three out of four patients who had measurable disease before the transplant experienced a complete response. We conclude that CD34-selected NMSCT followed by CD8-depleted DLI is feasible and preserves engraftment and apparently also the graft-versus-leukemia (GVL) effect. Further studies are needed to confirm this encouraging preliminary report.
Assuntos
Transplante de Medula Óssea , Rejeição de Enxerto/imunologia , Transplante de Células-Tronco Hematopoéticas , Linfócitos T/citologia , Quimeras de Transplante , Condicionamento Pré-Transplante/métodos , Adulto , Idoso , Antígenos CD34/análise , Transplante de Medula Óssea/efeitos adversos , Separação Celular , Estudos de Viabilidade , Rejeição de Enxerto/diagnóstico , Doença Enxerto-Hospedeiro/diagnóstico , Doença Enxerto-Hospedeiro/imunologia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Humanos , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Linfócitos T/químicaRESUMO
Cytogenetic analysis of rat hepatocarcinomas obtained after diethylnitrosamine (DEN) exposure showed a wide variety of numerical and structural chromosomal changes: 53 of 86 hepatocellular carcinomas showed at least one recurrent chromosomal aberration. Some of these recurrent changes occurred in several tumors. Chromosomes 1, 3, 11, and 12 were abnormal in more than 30% of the carcinomas; chromosomes 2, 4, 5, and 10 were abnormal in 10%. Moreover, chromosomes 1 and 10 were generally lost or deleted and chromosome 3, 4, and 11 were very often gained. The most frequent anomaly was loss of chromosome 1 which was observed in 35% of the tetraploid cell populations. The occurrence in several tumors of recurrent chromosomal rearrangements as well as various repeated aneuploidies strongly suggests that these anomalies are implicated in the process of rat hepatocarcinogenesis induced by DEN treatment.
Assuntos
Aberrações Cromossômicas , Dietilnitrosamina , Neoplasias Hepáticas Experimentais/genética , Animais , Deleção Cromossômica , Dietilnitrosamina/administração & dosagem , Cariotipagem , Neoplasias Hepáticas Experimentais/induzido quimicamente , Masculino , Ploidias , Ratos , Ratos EndogâmicosRESUMO
A patient with refractory anemia and a paracentric inversion of chromosome 12, inv(12)(q15q24), is described. This is the second reported case with this chromosome anomaly, suggesting that this rearrangement is a rare but nonrandom change associated with myelodysplastic syndromes.
Assuntos
Inversão Cromossômica , Cromossomos Humanos Par 12 , Síndromes Mielodisplásicas/genética , Idoso , Feminino , Humanos , CariotipagemRESUMO
Recently, Panoutsakopoulos et al. (1999) reported 2 cases of aneurysmal bone cysts with a recurrent (16;17)(q22;p13) translocation. We present here two additional cases harboring the same translocation as well as additional chromosomal changes.
Assuntos
Cistos Ósseos Aneurismáticos/genética , Aberrações Cromossômicas/genética , Cromossomos Humanos Par 16/genética , Cromossomos Humanos Par 17/genética , Translocação Genética , Cistos Ósseos Aneurismáticos/diagnóstico , Criança , Pré-Escolar , Bandeamento Cromossômico , Transtornos Cromossômicos , Feminino , Humanos , CariotipagemRESUMO
Translocation t(2p;3q) is a rare but recurrent finding in myeloid disorders. We present the first case of primary myelofibrosis with t(2;3)(p21;q26) as the sole chromosomal anomaly. The comparison with the 11 other previously published myeloid-associated t(2p;3q) cases confirms that this nonrandom translocation involves a pluripotent stem cell and is associated with a poor prognosis.
Assuntos
Cromossomos Humanos Par 2 , Cromossomos Humanos Par 3 , Mielofibrose Primária/genética , Translocação Genética , Idoso , Humanos , MasculinoRESUMO
Marrow dysplasia is a major characteristic of patients with myelodysplastic syndrome (MDS), along with marrow blastosis, cytopenia and cytogenetic anomalies. However, the impact of the degree of marrow dysplasia on survival has not been fully assessed. In this retrospective analysis of 111 patients selected according to the IPSS criteria of MDS diagnosis, the presence or absence of 21 dysplasia characteristics recognizable in bone marrow smears stained by the May-Grünwald-Giemsa method was correlated with patient survival. Using Cox proportional hazards regression analysis, megaloblastosis (MEGALO), neutrophil agranularity (AGRAN) and hypogranularity (HYPOGRAN) were highly significant predictors (p < 0.005), and Pelger-Huët anomaly (PELGHUET) a significant predictor (p = 0.05), of patient survival. The regression analysis yielded a dysplasia-based risk index (DI) where DI = 1.26 MEGALO + 0.82 AGRAN - 1.08 HYPOGRAN + 0.45 PELGHUET. The two subgroups of 60 and 47 patients with DI < or = 0 and > 0 showed highly significant differences in median survivals (2.6 vs 1.1 yrs; p <0.0001). Multivariate analysis further showed that DI offered additional predictive power that was independent of that provided by the IPSS (p=0.002 and 0.001 respectively). Analysis of survival curves stratified for IPSS and DI showed that the additional predictive power offered by inclusion of the DI essentially concerned the IPSS low/INT-1 risk categories. Further stratification for age did not improve survival prediction. The data indicate that a set of 4 dysplasia parameters can offer some prediction for survival of MDS patients in addition to that provided by the IPSS. Further multicenter studies should aim at including some form of evaluation of the degree of dysplasia in prognostic systems.
Assuntos
Medula Óssea/patologia , Síndromes Mielodisplásicas/patologia , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Síndromes Mielodisplásicas/mortalidade , Síndromes Mielodisplásicas/fisiopatologia , Valor Preditivo dos Testes , Prognóstico , Análise de SobrevidaRESUMO
Cytogenetic endpoints such as sister-chromatid exchanges (SCEs), chromosomal aberrations and micronuclei (MNs) have been widely used as indicators of genetic damage. However, no systematic attempts have been made to correlate the levels of these cytogenetic endpoints with the different steps of carcinogenesis. In the present report, the induction, accumulation and persistence of SCEs and high frequency cells (HFCs) were measured in liver cells during the initiation, promotion and progression steps of rat hepatocarcinogenesis induced by diethylnitrosamine (DEN). The results indicate that lesions leading to SCEs accumulate during initiation only. When DEN administration is longer than the duration of this first step, SCE values stabilize. After stopping the carcinogenic treatment, the SCE levels decrease to control values whether or not promotion and progression occur.
Assuntos
Dietilnitrosamina/farmacologia , Neoplasias Hepáticas Experimentais/genética , Troca de Cromátide Irmã/efeitos dos fármacos , Animais , Transformação Celular Neoplásica , Neoplasias Hepáticas Experimentais/induzido quimicamente , Neoplasias Hepáticas Experimentais/patologia , Masculino , Ratos , Ratos WistarRESUMO
We reported in our companion paper the strong correlation between elevated sister-chromatid exchange (SCE) frequencies and the initiation step of rat hepatocarcinogenesis. We have also shown that SCEs return to normal values during the promotion and the progression stages. In the present study, we evaluated the clastogenic activity of diethylnitrosamine (DEN) during initiation, promotion and progression of rat hepatocarcinogenesis. We measured, at various times after DEN administration, the number of micronuclei (MN) produced by the mitotic response to partial hepatectomy. The results established that the DEN treatment induces a great number of preclastogenic lesions. In subcarcinogenic conditions (initiation alone), the number of MN expressed after partial hepatectomy remains high regardless of the time interval between the end of the DEN treatment and the operation. In this condition, the preclastogenic lesions persist for up to 1 year after the DEN administration is discontinued. Conversely, in carcinogenic conditions (initiation + promotion + progression), the number of MN expressed after partial hepatectomy decreases during the promotion and progression stages. These observations indicate that promotion and progression but not initiation are associated with the expression of persistent preclastogenic lesions, resulting in the production of chromosomally abnormal hepatocytes.
Assuntos
Aberrações Cromossômicas , Dietilnitrosamina/farmacologia , Neoplasias Hepáticas Experimentais/genética , Animais , Transformação Celular Neoplásica , Hepatectomia , Neoplasias Hepáticas Experimentais/induzido quimicamente , Neoplasias Hepáticas Experimentais/patologia , Masculino , Testes para Micronúcleos , Índice Mitótico/efeitos dos fármacos , Ratos , Ratos WistarRESUMO
The circadian control of cell Proliferation and Differentiation has been studied principally in rat liver. The comparison between the differentiation by hepatic enzymes and the division by the cell cycle under various experimental conditions (postnatal maturation, regeneration after partial hepatectomy, adrenalectomy, corticosterone treatments etc.) leads to the following conclusions: Under physiological conditions, proliferation and differentiation activities present a mutually exclusive relationship with a specific circadian rhythm. For both functions, the circadian variation of corticosterone plays the role of synchronizer, each evening (peak) it induces the synthesis of tissue specific enzymes in G0 cells and simultaneously inhibits the DNA synthesis in cycling cells. The same parameters have been studied during the different stages of hepatocarcinogenesis induced by Diethylnitrosamine (DEN). After initiation alone, (DEN for 2 weeks) circadian control is unchanged and precancerous cells are not able to reach malignancy. Promotion (DEN for 6 weeks) consists of disturbing the circadian synchronization to liberate the selective growth of initiated precancerous cells. This proliferation advantage favours the accumulation of chromosomal aberrations including those implicated in malignant transformation: i.e. activation of oncogenes or inhibition of antioncogenes.
Assuntos
Neoplasias Hepáticas/fisiopatologia , Fígado/citologia , Animais , Divisão Celular , Células , Fenômenos Cronobiológicos , Ritmo Circadiano , Humanos , Cinética , Fígado/fisiologia , RatosRESUMO
Described in the present paper is a cytogenetic study of bovine oocytes matured in vitro. The cumulus-oocyte complexes (COC), punctured from ovaries recovered in a local slaughterhouse, were classified into 3 groups according to follicular diameter 1 to 4mm, 5 to 8mm and 9 to 13 mm. Metaphases available for observation were classified as metaphase I, haploid and diploid metaphase II. High levels of haploid metaphases II (90.6, 86.9 and 94.4 %) among the 3 groups of follicular sizes indicated successful meiotic resumption during in vitro maturation and suggested that cytoplasmic maturation may be responsible for low developmental rate after IVM, IVF and in vitro development (IVD).
RESUMO
We report a severely mentally retarded, dysmorphic girl aged 7 years with a 47,XX, +der(18), t(10;18)(p11.2;q11.2)mat. The phenotype of our patient is compared with 6 cases of trisomy 10p and 10 cases of trisomy 18q- from the literature. The short trisomic segment 10pter-10p11 appears to affect more the phenotype than the trisomic segment 18qter-q11.
Assuntos
Anormalidades Múltiplas/genética , Cromossomos Humanos Par 10 , Cromossomos Humanos Par 18 , Deficiência Intelectual/genética , Trissomia/genética , Criança , Feminino , Humanos , Cariotipagem , FenótipoRESUMO
A newborn male presenting with a peculiar appearance, hypertonia, a flexum attitude, hypospadias and skeletal abnormalities was found to bear a r 9 chromosome. A phenotypic distinction between early and late presenting forms is discussed.
Assuntos
Aberrações Cromossômicas , Cromossomos Humanos Par 9 , Face/anormalidades , Hipospadia/genética , Anormalidades Musculoesqueléticas , Humanos , Hipospadia/diagnóstico , Lactente , Recém-NascidoRESUMO
A 51-year old patient consults for abdominal swelling and persistent constipation. Clinical exploration shows the presence of a left iliac fossa tumor corresponding to a papillary serous adenocarcinoma of the fallopian tube after macroscopic and microscopic examination. The diagnostic and therapeutic problems caused by this rare gynecologic tumor are discussed.
Assuntos
Adenocarcinoma/patologia , Constipação Intestinal/etiologia , Neoplasias das Tubas Uterinas/patologia , Abdome/patologia , Adenocarcinoma/diagnóstico , Adenocarcinoma/cirurgia , Neoplasias das Tubas Uterinas/diagnóstico , Neoplasias das Tubas Uterinas/cirurgia , Feminino , Humanos , Pessoa de Meia-IdadeRESUMO
The myelodysplastic syndromes (MDS) are a heterogeneous group of disorders characterized by peripheral blood cytopenias with a hypercellular bone marrow exhibiting dyspoiesis. The predominant in elderly patients are associated with a high risk of progression to acute myelogenous leukemia. The etiology of MDS is unknown in most cases. About 10% of MDSs are secondary. MDS are classified by the French American British (FAB) classification into five subgroups. The incidence of the disorders is difficult to estimate but it seems to be increasing. Clonal cytogenetic aberrations are found in 30 to 50% of de novo MDS. The only currative treatment for MDS is allogeneic bone marrow transplantation.