RESUMO
INTRODUCCIÓN El linfoma de células del manto (LCM) es una neoplasia linfoide de células B correspondiente a alrededor del 7% de los linfomas no-Hodgkin. Los genes SOX4, SOX11 y SOX12 integran la familia SOXC involucrada en la neurogénesis embrionaria y el remodelado tisular. Entre ellos, SOX11 muestra expresión aberrante en LCM y se considera como un marcador molecular de pronóstico adverso. Diferentes estudios han mostrado un rol oncogénico del clúster miR17-92: miR17, miR18, miR19 y miR92 en neoplasias hematológicas, y hay escasa información sobre su asociación con LCM. OBJETIVOS Analizar los perfiles de expresión génica de los genes SOXC y su correlación con la expresión de los miembros del clúster miR-17-92 miR17, miR18, miR19 y miR92, en pacientes con LCM. MÉTODOS Se analizaron biopsias incluidas en parafina de 45 pacientes con LCM mediante PCR en tiempo real con metodología TaqMan, y 12 controles. Se evaluó el índice de proliferación con el marcador Ki67 por inmunohistoquímica. RESULTADOS Se detectó un aumento significativo de la expresión génica de SOX11 y SOX12 (2,1±0,24 y 3,1±0,16, respectivamente) respecto de SOX4 (1,2±0,21) (p=0,006 y p<0,0001, respectivamente), con una relación inversa entre los niveles de SOX11 y SOX4 (p=0,0017), siendo este último nulo en los pacientes con mayor expresión de SOX11. El análisis del clúster miR-17-92 mostró un aumento de expresión en miR19a (3,24±0,1) y miR92a (2,59±0,1) respecto de miR17 (-2,7±0,15) y miR18a (-2,8±0,19) (p<0,0001), así como una correlación positiva de miR92a con los restantes genes de este clúster (p<0,0013). Se halló una correlación positiva entre la expresión del clúster SOXC y miR18 (p<0,012). DISCUSIÓN Estos datos muestran por primera vez una correlación inversa entre la expresión de SOX11 y SOX4, así como una expresión diferencial de los genes SOXC y miR18, lo que sugiere una interacción de probable importancia biológica en LCM.
Assuntos
Expressão Gênica , Linfoma de Célula do MantoRESUMO
Chromosome abnormalities detected in metaphases from multiple myeloma (MM) cells have a clear impact on prognosis and response to therapy. Thirteen out of 50 (26%) patients with plasma cell disorders and abnormal karyotypes (11 with MM and 2 with plasma cell leukemia (PCL)) were selected for inclusion in the present report based on the presence of karyotypes with new and/or infrequent structural aberrations. Thirty-three new rearrangements, including a novel recurrent aberration: psu dic(5;1)(q35;q10), were detected. Chromosome 1 was the most frequently involved. Gains of genetic material (57%) were noted more frequently than losses (43%). Three rearrangements that were observed only once in the literature appear to be recurrent from our data: del(16)(q13), del(5)(p13) and i(3)(q10), the latter being a single structural aberration in the karyotype. Clinical parameters from our series were compared with 2 control groups: 20 MM cases with recurrent aberrations in MM/PCL with a similar distribution of abnormalities associated with poor prognosis (group 1), and 40 with normal karyotypes and fluorescence in situ hybridization analysis (group 2). Significantly increased serum calcium levels (p = 0.022) in patients with new and/or infrequent chromosome changes with respect to both control groups, and a higher percentage of bone marrow plasma cell infiltration (p = 0.005), ß(2) microglobulin, and lactate dehydrogenase levels (p < 0.0001) compared to group 2 were observed. Our results suggest that some of these novel rearrangements may be capable to deregulate genetic mechanisms related to the development and/or progression of the disease. The finding of new recurrent aberrations supports this hypothesis.
Assuntos
Aberrações Cromossômicas , Leucemia Plasmocitária/genética , Mieloma Múltiplo/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Cálcio/sangue , Cromossomos Humanos Par 1/genética , Cromossomos Humanos Par 16/genética , Cromossomos Humanos Par 3/genética , Cromossomos Humanos Par 5/genética , Feminino , Humanos , Hibridização in Situ Fluorescente , Cariotipagem , Leucemia Plasmocitária/sangue , Leucemia Plasmocitária/patologia , Masculino , Pessoa de Meia-Idade , Mieloma Múltiplo/sangue , Mieloma Múltiplo/patologia , PrognósticoRESUMO
Los telómeros son estructuras esenciales para el mantenimiento de la integridad cromosómica y la capacidad replicativa de la célula. La reducción de la longitud telomérica (LT) aumenta la probabilidad de producir errores capaces de generar cambios genómicos importantes para el desarrollo neoplásico, determinando desbalances de material genético. En este trabajo se evaluó la LT mediante el análisis de fragmentos de restricción terminal (TRF) en médula ósea y/o biopsia ganglionar de 36 pacientes (edad media: 54.2 años; rango 29-77 años; 21 varones): 29 con linfoma folicular (LF) al diagnóstico y 7 con linfoma B difuso a células grandes secundario a LF (LBDCG-S). Se efectuó el análisis del rearreglo molecular del gen BCL-2 por PCR anidada y de larga distancia. Las medias de TRF en LF (4.18±0.18 Kb) y LBDCG-S (3.31±0.25 Kb) resultaron significativamente menores que en controles (8.50±0.50 Kb) (p<0.001), encontrándose diferencias entre ambos subtipos histológicos (p=0.036). Las muestras negativas para el rearreglo BCL-2 mostraron LT menores (3.39±0.30 Kb) que las positivas (4.25±0.19 Kb) (p=0.023), observándose una tendencia a valores menores en pacientes negativos para el rearreglo BCL-2, intermedios en positivos para mcr, minor cluster region, (3.84±0.45 Kb) y mayores en los positivos para MBR, Major Breakpoint Region, (4.35±0.21 Kb). Nuestros resultados muestran una reducción de la LT en LF y LBDCG-S, con TRFs significativamente más cortos en estos últimos, sugiriendo la participación del acortamiento telomérico em la progresión tumoral. Asimismo, las diferencias detectadas entre los casos BCL-2 positivos y negativos sustentarían la presencia de diferentes mecanismos patogénicos propuestos para estos distintos LF.
Assuntos
Adulto , Pessoa de Meia-Idade , Humanos , Masculino , Feminino , Linfoma Difuso de Grandes Células B , Linfoma de Células B/genética , Linfoma Folicular/genética , Telômero/fisiologia , Medula Óssea/patologia , Gânglios/patologia , /genética , Telômero/genéticaRESUMO
Los telómeros son estructuras esenciales para el mantenimiento de la integridad cromosómica y la capacidad replicativa de la célula. La reducción de la longitud telomérica (LT) aumenta la probabilidad de producir errores capaces de generar cambios genómicos importantes para el desarrollo neoplásico, determinando desbalances de material genético. En este trabajo se evaluó la LT mediante el análisis de fragmentos de restricción terminal (TRF) en médula ósea y/o biopsia ganglionar de 36 pacientes (edad media: 54.2 años; rango 29-77 años; 21 varones): 29 con linfoma folicular (LF) al diagnóstico y 7 con linfoma B difuso a células grandes secundario a LF (LBDCG-S). Se efectuó el análisis del rearreglo molecular del gen BCL-2 por PCR anidada y de larga distancia. Las medias de TRF en LF (4.18±0.18 Kb) y LBDCG-S (3.31±0.25 Kb) resultaron significativamente menores que en controles (8.50±0.50 Kb) (p<0.001), encontrándose diferencias entre ambos subtipos histológicos (p=0.036). Las muestras negativas para el rearreglo BCL-2 mostraron LT menores (3.39±0.30 Kb) que las positivas (4.25±0.19 Kb) (p=0.023), observándose una tendencia a valores menores en pacientes negativos para el rearreglo BCL-2, intermedios en positivos para mcr, minor cluster region, (3.84±0.45 Kb) y mayores en los positivos para MBR, Major Breakpoint Region, (4.35±0.21 Kb). Nuestros resultados muestran una reducción de la LT en LF y LBDCG-S, con TRFs significativamente más cortos en estos últimos, sugiriendo la participación del acortamiento telomérico em la progresión tumoral. Asimismo, las diferencias detectadas entre los casos BCL-2 positivos y negativos sustentarían la presencia de diferentes mecanismos patogénicos propuestos para estos distintos LF. (AU)
Assuntos
Adulto , Pessoa de Meia-Idade , Idoso , Humanos , Masculino , Feminino , RESEARCH SUPPORT, NON-U.S. GOVT , Telômero/fisiologia , Linfoma Folicular/genética , Linfoma Difuso de Grandes Células B/genética , Linfoma de Células B/genética , Telômero/genética , Genes bcl-2/genética , Gânglios/patologia , Medula Óssea/patologiaRESUMO
Telomeres are specialized structures at the ends of eukaryotic chromosomes, composed of tandem repeats of a repetitive DNA sequence (TTAGGG)n and associated proteins. They have a number of important functions including the protection of chromosomes from end-to-end fusion and degradation. When telomeres become critically short, telomere separation in mitosis cannot be performed properly leading to metaphase telomeric associations (tas) and chromosome instability. This instability can be relevant for neoplastic transformation because it increases the probability of errors that can generate genetic changes critical in the multistep process of transformation, like gene amplification and loss of heterozygosity. The mechanisms involved in tas are unknown, but it could be because of failure in the enzymatic activity of telomerase, a ribonucleoprotein enzyme with an RNA template that directs synthesis of telomeric repeats at chromosome extremities, producing telomeric length stabilization. A progressive telomere shortening with ageing has been shown to occur both in vitro and in vivo. Recent studies have shown an association between the presence of tas and telomeric shortening, and also a correlation between telomere reduction and increased telomerase activity in both solid tumors and hematologic malignancies. The evidence that most human malignancies have telomerase activity would indicate that telomerase could be a prevalent and specific tumor marker, and thus may be a novel and excellent target for anti-cancer therapy.
Assuntos
Transformação Celular Neoplásica/metabolismo , Senescência Celular/fisiologia , Proteínas de Neoplasias/metabolismo , Neoplasias/enzimologia , Telomerase/metabolismo , Telômero/enzimologia , Neoplasias Hematológicas/enzimologia , Humanos , Neoplasias/etiologiaRESUMO
Telomeres are specialized structures at the ends of eukaryotic chromosomes, composed of tandem repeats of a repetitive DNA sequence (TTAGGG)n and associated proteins. They have a number of important functions including the protection of chromosomes from end-to-end fusion and degradation. When telomeres become critically short, telomere separation in mitosis cannot be performed properly leading to metaphase telomeric associations (tas) and chromosome instability. This instability can be relevant for neoplastic transformation because it increases the probability of errors that can generate genetic changes critical in the multistep process of transformation, like gene amplification and loss of heterozygosity. The mechanisms involved in tas are unknown, but it could be because of failure in the enzymatic activity of telomerase, a ribonucleoprotein enzyme with an RNA template that directs synthesis of telomeric repeats at chromosome extremities, producing telomeric length stabilization. A progressive telomere shortening with ageing has been shown to occur both in vitro and in vivo. Recent studies have shown an association between the presence of tas and telomeric shortening, and also a correlation between telomere reduction and increased telomerase activity in both solid tumors and hematologic malignancies. The evidence that most human malignancies have telomerase activity would indicate that telomerase could be a prevalent and specific tumor marker, and thus may be a novel and excellent target for anti-cancer therapy.
RESUMO
Translocation t(14; 18) has been observed in 50-85% of follicular and in 30% of diffuse non-Hodgkin lymphomas. About half of follicle center lymphoma (FCL) undergo histological conversion at relapse to more aggressive diffuse large B-cell lymphoma (DLBCL). This report correlates the molecular bcl-2/IgH rearrangement by PCR and Bcl-2 immunohistochemical (IHC) expression in a series of high grade DLBCLs with and without FCL remnant. Twenty-three paraffin-embedded lymph nodes from DLBCL patients were analyzed. Eleven patients showed FCL remnant (Group A) and 12, did not (Group B). Single PCR from paraffin extracted DNA followed by Southern transfer of products, hybridisation with internal oligoprobes for the MBR/JH and MCR/JH bcl-2 rearrangements and IHC analysis of Bcl-2 expression, were performed. PCR analysis was positive in 34.8% of patients. Bcl-2/IgH gene rearrangements were observed in 8 (34%) cases and 7 (30%) showed Bcl-2 expression on large noncleaved B-cells (centroblasts). All patients from Group A showed IHC positive reaction on FCL remnant (small cleaved cells) but only 2 (18%) were positive in DLBCL areas, suggesting either the loss of the bcl-2 expression on the transformed lymphoma, or, alternatively, the development of a second disease when the first lymphoma transforms. Group B patients showed a clear correlation between PCR and IHC studies. Our results suggest a similar frequency of t(14; 18) in DLBCLs to that reported in Europe and USA series. The discordance observed between PCR and IHC, particularly in Group A, points out the necessity to perform both studies in order to detect bcl-2 gene involvement in DLBCLs.
Assuntos
Genes bcl-2/genética , Linfoma Difuso de Grandes Células B/genética , Adulto , Idoso , DNA de Neoplasias/análise , Feminino , Rearranjo Gênico do Linfócito B , Humanos , Linfoma Difuso de Grandes Células B/patologia , Masculino , Pessoa de Meia-Idade , Análise de Sequência com Séries de Oligonucleotídeos , Inclusão em Parafina , Reação em Cadeia da PolimeraseRESUMO
OBJECTIVE: Chromosome instability provides a predisposing background to malignancy, contributing to the crucial genetic changes in multistep carcinogenesis. The aim of this work was to analyze chromosome instability in patients with ulcerative colitis (UC) to achieve a better understanding of the increased risk for colorectal cancer. METHODS: Peripheral blood lymphocyte cultures from 20 untreated UC patients and 24 controls were used to study chromosome instability by assessing telomeric associations (TAS), chromosome aberrations (CA), and sister chromatid exchanges (SCE). RESULTS: Mean frequencies of TAS and CA were significantly increased in UC patients compared to controls (p < 0.001). Chromosomes 10, 11, 21, 16, and 19 were the most frequently involved in TAS. A total of 104 CA clustered in 66 breakpoints could be exactly localized. Seven nonrandom bands significantly affected in UC patients were found (p < 0.004), showing a significant correlation with the location of cancer breakpoints (p < 0.003), particularly with colorectal carcinoma rearrangements. SCE analysis showed higher levels in patients compared to controls (p < 0.006), but no differences were observed in cell cycle kinetics. CONCLUSIONS: Our results demonstrate the presence of an unstable genome in UC patients that could be related to the cancer development observed in this disease.
Assuntos
Aberrações Cromossômicas/genética , Colite Ulcerativa/genética , Frequência do Gene/genética , Troca de Cromátide Irmã/genética , Telômero/genética , Adolescente , Adulto , Idoso , Biópsia , Ciclo Celular/genética , Células Cultivadas , Colite Ulcerativa/complicações , Colite Ulcerativa/patologia , Colonoscopia , Neoplasias Colorretais/etiologia , Neoplasias Colorretais/genética , Feminino , Marcadores Genéticos , Predisposição Genética para Doença , Humanos , Masculino , Pessoa de Meia-Idade , Telômero/ultraestruturaAssuntos
Análise Citogenética , Cromossomo Filadélfia , Translocação Genética , Adulto , Cromossomos Humanos Par 22 , Cromossomos Humanos Par 9 , Proteínas de Fusão bcr-abl/genética , Variação Genética , Humanos , Cariotipagem , Leucemia Mielogênica Crônica BCR-ABL Positiva/genética , Masculino , Pessoa de Meia-IdadeRESUMO
Intron 22 factor VIII gene inversion (Inv22) is the most common mutation causing severe haemophilia A (SHA). We studied Inv22 in 34 SHA affected families by Southern blotting. Data from the familial history of the disease and the inhibitor status were also included. We found Inv22 in 41 % of SHA Argentine families (35 % with type 1 and 6 % with type 2), in close agreement with previously reported series. No significant correlation between the inheritance (familiar or sporadic disease) and the presence of inversions was found. Our population showed 24 % of families included at least one hemophiliac with inhibitor. In families positive for Inv22, 29 % of patients developed inhibitor but this increased frequency was not statistically significant. In conclusion, analysis of Inv22 in SHA patients should be used as a first line method because it provides useful and secure information for carrier detection and prenatal diagnosis in a high percentage of cases.
Assuntos
Inversão Cromossômica , Fator VIII/genética , Hemofilia A/genética , Íntrons/genética , Argentina/epidemiologia , Southern Blotting , Sondas de DNA , Fator VIII/imunologia , Saúde da Família , Feminino , Frequência do Gene , Hemofilia A/epidemiologia , Hemofilia A/imunologia , Humanos , Isoanticorpos/sangue , Masculino , Polimorfismo de Fragmento de RestriçãoRESUMO
In the current study we analyzed chromosome instability on peripheral blood lymphocytes cultured from 7 untreated patients with chronic pancreatitis (CP) by assessing telomeric associations (TAS), chromosome aberrations (CA) and sister chromatid exchanges (SCE). Seven healthy individuals were also analyzed. Mean frequencies of TAS were significantly higher in CP patients (X +/- SE: 11.00 +/- 2.37) compared to controls (1.00 +/- 0.30) (p<0.001). Chromosomes preferentially involved in TAS were: 9, 20, 16 and 21, being the most affected arms: 9p, 20q, 16p, 9q and 21q. All these terminal bands were coincident with cancer breakpoints (p<0.03), two of them (40%) were specifically associated to pancreatic carcinoma rearrangements. Three bands (60%) were coincident with oncogene location. The mean frequency of CA was significantly higher in patients (3.88 +/- 0.80) compared to controls (0.63 +/- 0.49) (p<0.001). Chromosomes 1, 2 and 13 were the most damaged. No specifically affected breakpoints were found. SCE analysis showed higher levels in patients (8.33 +/- 0.70) than in controls (6.62 +/- 0.34) (p<0.025), but no differences were observed in cell cycle kinetics. Our results clearly indicate that CP patients exhibit chromosome instability, showing the presence of an unstable genome that could be related to the cancer development observed in this disease.
Assuntos
Aberrações Cromossômicas , Mapeamento Cromossômico , Pancreatite/genética , Troca de Cromátide Irmã , Idoso , Idoso de 80 Anos ou mais , Células Cultivadas , Cromossomos Humanos Par 16 , Cromossomos Humanos Par 20 , Cromossomos Humanos Par 21 , Cromossomos Humanos Par 9 , Doença Crônica , Feminino , Humanos , Linfócitos/patologia , Masculino , Pessoa de Meia-Idade , Pancreatite/sangue , Pancreatite/patologiaRESUMO
Cases with partial trisomy 12 have rarely been found in B-cell chronic lymphocytic leukemia (CLL). We report our clinical, cytogenetic and fluorescence in situ hybridization (FISH) findings in a CLL patient with a duplication of part of the long arm of chromosome 12 between bands q13-q22. This patient was the only case with this duplication among the 112 cases (0.9%) of CLL cytogenetically analyzed in our laboratory. FISH studies using unique-sequence specific probes for the RB-1 (retinoblastoma) gene and the D13S319 locus at the 13q14 band showed a monoallelic loss for the D13S319 locus (20% of cells) with a diploid RB-1 gene. Our case showed an atypical morphology (35% prolymphocytes), a high proliferation rate and progression of the disease, indicating that the duplication of this region may be equivalent to complete trisomy 12 in CLL patients.
Assuntos
Cromossomos Humanos Par 12/genética , Cromossomos Humanos Par 13/genética , Deleção de Genes , Duplicação Gênica , Leucemia Linfocítica Crônica de Células B/genética , Idoso , Alelos , Divisão Celular/genética , Análise Citogenética , Progressão da Doença , Feminino , Humanos , Imunofenotipagem , Hibridização in Situ Fluorescente , Leucemia Linfocítica Crônica de Células B/etiologia , Leucemia Linfocítica Crônica de Células B/patologia , Retinoblastoma/genética , TrissomiaRESUMO
Translocation t(14; 18) has been observed in 50-85
of follicular and in 30
of diffuse non-Hodgkin lymphomas. About half of follicle center lymphoma (FCL) undergo histological conversion at relapse to more aggressive diffuse large B-cell lymphoma (DLBCL). This report correlates the molecular bcl-2/IgH rearrangement by PCR and Bcl-2 immunohistochemical (IHC) expression in a series of high grade DLBCLs with and without FCL remnant. Twenty-three paraffin-embedded lymph nodes from DLBCL patients were analyzed. Eleven patients showed FCL remnant (Group A) and 12, did not (Group B). Single PCR from paraffin extracted DNA followed by Southern transfer of products, hybridisation with internal oligoprobes for the MBR/JH and MCR/JH bcl-2 rearrangements and IHC analysis of Bcl-2 expression, were performed. PCR analysis was positive in 34.8
of patients. Bcl-2/IgH gene rearrangements were observed in 8 (34
) cases and 7 (30
) showed Bcl-2 expression on large noncleaved B-cells (centroblasts). All patients from Group A showed IHC positive reaction on FCL remnant (small cleaved cells) but only 2 (18
) were positive in DLBCL areas, suggesting either the loss of the bcl-2 expression on the transformed lymphoma, or, alternatively, the development of a second disease when the first lymphoma transforms. Group B patients showed a clear correlation between PCR and IHC studies. Our results suggest a similar frequency of t(14; 18) in DLBCLs to that reported in Europe and USA series. The discordance observed between PCR and IHC, particularly in Group A, points out the necessity to perform both studies in order to detect bcl-2 gene involvement in DLBCLs.
Assuntos
Anormalidades Múltiplas/genética , Aneuploidia , Cromossomos Humanos Par 21 , Anormalidades Múltiplas/patologia , Criança , Bandeamento Cromossômico , Humanos , Recém-Nascido , Deficiência Intelectual/genética , Cariotipagem , Masculino , Hibridização de Ácido Nucleico , Fenótipo , Puberdade PrecoceRESUMO
We report a case of B-cell chronic lymphocytic leukemia (B-CLL) with aberrant expression of the T-cell-associated antigen CD8, as revealed by two-color flow-cytometric analysis. DNA studies showed immunoglobulin heavy-chain gene rearrangement, but not of gamma-chain T-cell receptor, confirming the B-cell origin of the neoplastic cells. Ploidy analysis showed a tetraploid population and high S-phase fraction. B-CLL cells also carried trisomy 12, detected by fluorescence in situ hybridization. The identification of more cases with the same features would be necessary to establish the prognosis of this subtype of B-CLL.
Assuntos
Antígenos CD8/biossíntese , Cromossomos Humanos Par 12 , Leucemia Linfocítica Crônica de Células B/imunologia , Trissomia , Idoso , Humanos , Leucemia Linfocítica Crônica de Células B/genética , MasculinoRESUMO
We have studied an extra structually abnormal chromosome (ESAC) in a 13 years old boy with profound mental, psychomotor and speech retardation, behavioral problems, seizures and abnormal electroencephalogram. The examination of the bisatellited ESAC with chromosome banding demonstrated that the karyotype was: 47, XY, +inv dup (15) (pter-->q13::q13-->pter). The cytogenetic characterization of the inv dup (15) is reported with special emphasis on the usefulness of DA/DAPI staining when G-banding is sequentially performed to discard possible heteromorphisms in DA/DAPI positive chromosomes, and the importance of Ag-NOR heteromorphisms to ascertain the maternal origin of the inv dup (15). A U-type exchange between two non-sister chromatids is proposed as its mechanism of formation. The clinical features of the case were consistent with those previously reported in similar cases.
Assuntos
Aberrações Cromossômicas , Inversão Cromossômica , Cromossomos Humanos Par 15 , Deficiência Intelectual/genética , Adolescente , Bandeamento Cromossômico , Mapeamento Cromossômico , Duplicação Gênica , Humanos , Deficiência Intelectual/patologia , Cariotipagem , Masculino , Transtornos Mentais/genética , Convulsões/genética , Distúrbios da Fala/genéticaRESUMO
AIMS: To present data obtained from human bone marrow preparations from healthy individual showing that the proportion of metaphases with silver stained nucleolar organiser region (AgNOR) chromosomes is associated with the age of the donor. METHODS: Bone marrow preparations from eight Russian and 10 Argentinian healthy individuals donating bone marrow for heterologous transplantation were studied by silver staining. The Russian bone marrow preparations were used directly, while the bone marrow specimens from Argentinian donors were incubated for 24 hours at 37 degrees C in F-10 medium with 15% fetal bovine serum. The slides were silver stained by the one step method of Howell and Black with slight modifications. Thirty metaphases with clearly defined D and G group chromosomes were scored for the numbers of AgNORs. All metaphases that were adjacent to silver stained interphase nuclei were analysed to assess the percentage of AgNOR positive mitoses. The Kruskal Wallis test and Kendall's rank correlation coefficient (rK) were used to assess the relation between age and the percentage of AgNOR positive cells. RESULTS: The mean numbers (SE) of AgNORs per metaphase were 5.06 (0.17) and 5.56 (0.23) for the Russian and Argentinian groups, respectively, with no significant differences between the two groups. The common percentage of AgNOR positive cells decreased significantly as a function of age, with an rK = -0.57 (p < 0.0012). CONCLUSIONS: The percentages of AgNOR negative metaphases in bone marrow from healthy individuals is strongly associated with age and this may be related to age related telomere loss.
Assuntos
Envelhecimento/genética , Cromossomos Humanos 13-15 , Cromossomos Humanos 21-22 e Y , Região Organizadora do Nucléolo/genética , Adolescente , Adulto , Células da Medula Óssea/ultraestrutura , Criança , Feminino , Humanos , Masculino , Metáfase/genética , Pessoa de Meia-Idade , Mitose/genética , Coloração pela PrataRESUMO
It has been suggested that genetic predisposition to cancer might be related to spontaneous chromosome instability or to fragile site expression. Therefore, spontaneous breakage and fragile sites were analyzed in nine untreated chronic lymphocytic leukemia (CLL) patients to determine their relation to cancer rearrangements. Five cases presented spontaneous gaps and breaks with a random distribution of breakpoints. In cultures treated with fluorodeoxyuridine or aphidicolin, 29 specific bands could be defined as fragile sites. A significant clustering of these sites was found with known common fragile sites (c-fra) and cancer breakpoints described in the literature. Most of these cancer breakpoints were involved in structural abnormalities associated with CLL (p < 0.00001). These data suggest that the expression of specific fragile sites might be related to structural chromosomal aberrations in CLL.
Assuntos
Quebra Cromossômica/genética , Fragilidade Cromossômica , Leucemia Linfocítica Crônica de Células B/genética , Idoso , Afidicolina , Sítios Frágeis do Cromossomo , Mapeamento Cromossômico , Feminino , Floxuridina , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Leucemia Linfocítica Crônica de Células B/patologia , Masculino , Pessoa de Meia-Idade , Células Tumorais CultivadasRESUMO
IIB-BR-G is an undifferentiated, highly heterogeneous, hormone receptor negative human breast cancer cell line previously established in our laboratory from a patient's primary tumor. An in vitro growing cell line (IIB-BR-G) and a xenotransplanted tumor growing in nude mice (IIB-BR-G(NUDE)) were derived. To further characterize these systems, immunocytochemical analysis was performed for differentiation antigens (PEM 200 kDa, CEA, NCA 90 kDa), blood-group related antigens (Le(x), sTn), oncogenes and tumor suppressor gene products (Her-2/neu protein, p53), metastasis-related cathepsin D and CD63/5.01 Ag, and the chemokine monocyte chemotactic protein 1 (MCP-1). Expression of markers was heterogeneous in these different systems. Previously reported karyotypic analysis has shown extensive chromosomal alterations including double min. Searching for oncogene amplification, we detected augmented copy number of c-myc and c-fos, the last one with two rearranged fragments. No amplification was found for c-erbB-2 in the cell line or in IIB-BR-G(NUDE), although this oncogene was amplified in the patient's primary tumor DNA. The differences observed between the patient's tumor, the cell line and the IIB-BR-G(NUDE) tumors are probably due to clonal expansion of cell variants not present in the original tumor. Electron microscopy of IIB-BR-G growing cells revealed epithelial characteristics with abundant dense granules, presumably secretory, distributed all over the cytoplasm and great nuclear pleomorphism. In vitro, IIB-BR-G cells showed a significant number of invading cells by Matrigel assay. After nearly 40 sequential subcutaneous passages of the original xenograft through nude mice, 80% of recipients developed spontaneous metastases, primarily to the lung and lymph nodes. Since this experimental model allowed to analyze changes produced in cancer cells from the primary tumor during adaptation to in vitro and in vivo growth, our results provide novel insights on the behaviour of hormone independent metastatic breast cancer.
Assuntos
Proteínas Proto-Oncogênicas c-fos/genética , Proteínas Proto-Oncogênicas c-myc/genética , Animais , Antígenos de Neoplasias/biossíntese , Neoplasias da Mama , Carcinoma Ductal de Mama , Feminino , Amplificação de Genes , Humanos , Camundongos , Camundongos Nus , Invasividade Neoplásica , Receptores de Estrogênio/genética , Transplante Heterólogo , Células Tumorais CultivadasRESUMO
Chromosome banding studies carried out on bone marrow cells from a 16 year-old boy with an M1 acute nonlymphocytic leukemia (ANLL) revealed an unbalanced translocation involving chromosomes 1 and 10: der(10) t(1;10) (q21;q26) that results in a partial trisomy 1q between bands 1q21-1qter. Marker del(6)(q21) and trisomies of chromosomes 18, 21 and 22 were also observed. To our knowledge, this der(10) is the first to be reported in a patient with ANLL.
