Asunto(s)
Cromosomas Humanos Par 19/genética , Cromosomas Humanos Par 22/genética , Infecciones por Virus de Epstein-Barr/genética , Translocación Genética , Cariotipo Anormal , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Linfocitos B/química , Linfocitos B/virología , Cromosomas Humanos Par 19/ultraestructura , Cromosomas Humanos Par 22/ultraestructura , Cisplatino/administración & dosificación , Ciclofosfamida/administración & dosificación , Citarabina/administración & dosificación , Doxorrubicina/administración & dosificación , Etopósido/administración & dosificación , Humanos , Linfoma de Células B Grandes Difuso/virología , Masculino , Metilprednisolona/administración & dosificación , Prednisona/administración & dosificación , ARN Neoplásico/análisis , ARN Viral/análisis , Rituximab/administración & dosificación , Vincristina/administración & dosificaciónRESUMEN
This report describes a newborn girl presenting with some of the common features of DiGeorge syndrome/velocardiofacial syndrome (DGS/VCFS), including hypocalcemia, atrial septal defect, and aortic stenosis. Several genetic tests were carried out to determine the origin of the clinical phenotype. MLPA was initially performed followed by aCGH, cytogenetic analysis, and FISH. Cytogenetic analysis of the proband's parents was also done. MLPA revealed a deletion in 22q11.1q11.2 spanning from the cat eye syndrome region to the most commonly deleted region in DGS/VCFS patients. The size of the deletion as defined by aCGH was 3.2 Mb. The karyotype of the proband was 45,XX,der(1)t(1;22)(p36.3;q11.2)dn,-22, the karyotypes of the parents were normal. FISH analysis showed that the 22q11 deletion occurred in the der(1). No loss or gain of chromosomal material was evident for chromosome 1, as confirmed by MLPA, aCGH, and FISH. Unbalanced translocations resulting in DGS are relatively rare, with limited reports in the literature. To our knowledge, this is the second case involving chromosome 1 and the first one with breakpoints in 1p36 and 22q11.2. This case also emphasizes the importance of combining diagnostic methods to better understand a given genetic abnormality.
Asunto(s)
Síndrome de Deleción 22q11/genética , Cromosomas Humanos Par 1/genética , Cromosomas Humanos Par 22/genética , Eliminación de Secuencia , Translocación Genética/genética , Cariotipo Anormal , Cromosomas Humanos Par 1/ultraestructura , Cromosomas Humanos Par 22/ultraestructura , Hibridación Genómica Comparativa , Síndrome de DiGeorge/genética , Femenino , Humanos , Hibridación Fluorescente in Situ , Recién Nacido , Técnicas de Amplificación de Ácido Nucleico , SíndromeRESUMEN
Chronic Myeloid Leukemia (CML) is myeloproliferative neoplasm characterized by Philadelphia chromosome which is a balanced translocation between chromosome 9 and 22 in 90% of cases. However, variant cytogenetic still happens in 5-10 % of cases, the importance of which is controversial as well as its response to therapy, prognosis and progression to acute leukemias. Here we report a male patient with CML and variant cytogenetic who responded to low dose of Dasatinib (50 mg daily).
Asunto(s)
Cariotipo Anormal , Leucemia Mielógena Crónica BCR-ABL Positiva/genética , Translocación Genética , Antineoplásicos/uso terapéutico , Médula Ósea/patología , Aberraciones Cromosómicas , Cromosomas Humanos Par 17/genética , Cromosomas Humanos Par 17/ultraestructura , Cromosomas Humanos Par 22/genética , Cromosomas Humanos Par 22/ultraestructura , Cromosomas Humanos Par 9/genética , Cromosomas Humanos Par 9/ultraestructura , Dasatinib/uso terapéutico , Humanos , Hibridación Fluorescente in Situ , Leucemia Mielógena Crónica BCR-ABL Positiva/tratamiento farmacológico , Leucemia Mielógena Crónica BCR-ABL Positiva/patología , Masculino , Persona de Mediana Edad , Terapia Molecular Dirigida , Inhibidores de Proteínas Quinasas/uso terapéuticoRESUMEN
We describe a delayed diagnosis of Di George syndrome, in a 51 yr-old woman, with past medical history of epilepsy, mental retardation, chronic psychosis, nephrocalcinosis. She presented facial dysmorphism, multiple encephalic calcifications, hypocalcemia and lymphopenia. A microdeletion of 22q 11.2 was detected by fluorescence in situ hybridization (FISH), confirming the clinical suspicion .
Asunto(s)
Diagnóstico Tardío , Síndrome de DiGeorge/diagnóstico , Anomalías Múltiples/etiología , Encefalopatías Metabólicas/diagnóstico por imagen , Encefalopatías Metabólicas/etiología , Calcinosis/diagnóstico por imagen , Calcinosis/etiología , Deleción Cromosómica , Cromosomas Humanos Par 22/ultraestructura , Síndrome de DiGeorge/genética , Síndrome de DiGeorge/metabolismo , Síndrome de DiGeorge/psicología , Epilepsia/etiología , Femenino , Heterocigoto , Humanos , Hipocalcemia/tratamiento farmacológico , Hipocalcemia/etiología , Hipoparatiroidismo/etiología , Discapacidad Intelectual/etiología , Persona de Mediana Edad , Trastornos Psicóticos/etiología , RadiografíaAsunto(s)
Linfoma de Células B/patología , Anciano , Biomarcadores de Tumor/análisis , Biopsia , Linfoma de Burkitt/diagnóstico , Tamaño de la Célula , Cromosomas Humanos Par 14/genética , Cromosomas Humanos Par 14/ultraestructura , Cromosomas Humanos Par 18/genética , Cromosomas Humanos Par 18/ultraestructura , Cromosomas Humanos Par 22/genética , Cromosomas Humanos Par 22/ultraestructura , Cromosomas Humanos Par 8/genética , Cromosomas Humanos Par 8/ultraestructura , Evolución Clonal , Diagnóstico Diferencial , Genes bcl-2 , Genes myc , Centro Germinal/patología , Humanos , Inmunofenotipificación , L-Lactato Deshidrogenasa/análisis , Linfoma de Células B/química , Linfoma de Células B/clasificación , Linfoma de Células B/diagnóstico , Linfoma de Células B/genética , Linfoma de Células B Grandes Difuso/diagnóstico , Masculino , Invasividad Neoplásica , Leucemia-Linfoma Linfoblástico de Células Precursoras/diagnóstico , Leucemia-Linfoma Linfoblástico de Células Precursoras/patología , Translocación GenéticaAsunto(s)
Dermatofibrosarcoma/secundario , Neoplasias del Mediastino/secundario , Biomarcadores de Tumor/análisis , Biopsia con Aguja Fina , Broncoscopía , Cromosomas Humanos Par 17/ultraestructura , Cromosomas Humanos Par 22/ultraestructura , Dermatofibrosarcoma/química , Dermatofibrosarcoma/diagnóstico por imagen , Dermatofibrosarcoma/genética , Dermatofibrosarcoma/cirugía , Humanos , Masculino , Neoplasias del Mediastino/química , Neoplasias del Mediastino/diagnóstico por imagen , Persona de Mediana Edad , Proteínas de Neoplasias/análisis , Hombro , Neoplasias Cutáneas/química , Neoplasias Cutáneas/genética , Neoplasias Cutáneas/patología , Neoplasias Cutáneas/cirugía , Tomografía Computarizada por Rayos X , Translocación GenéticaRESUMEN
We report a 40-year-old man who was found to have profound hypocalcaemia and hypoparathyroidism when investigated for multiple, generalized, tonic/clonic seizures and a chest infection. Computed tomography scan of the brain revealed extensive symmetric bilateral calcification within the cerebellum, thalamus and basal ganglia. Molecular cytogenetic testing by fluorescent in situ hybridization using the commercial Vysis LSI DiGeorge/VCFS dual colour probe set showed a deletion of 22q11.2. The extraordinary feature of this case is the adult presentation of hypocalcaemia, hypoparathyroidism and basal ganglia calcification due to 22q11.2 deletion.
Asunto(s)
Ganglios Basales/patología , Calcinosis/genética , Deleción Cromosómica , Cromosomas Humanos Par 22/ultraestructura , Síndrome de DiGeorge/diagnóstico , Epilepsia Tónico-Clónica/etiología , Hipocalcemia/genética , Hipoparatiroidismo/genética , Adulto , Edad de Inicio , Anticonvulsivantes/uso terapéutico , Ganglios Basales/diagnóstico por imagen , Encéfalo/diagnóstico por imagen , Encéfalo/patología , Calcinosis/diagnóstico por imagen , Calcinosis/patología , Síndrome de DiGeorge/clasificación , Síndrome de DiGeorge/epidemiología , Síndrome de DiGeorge/genética , Epilepsia Tónico-Clónica/tratamiento farmacológico , Humanos , Hiperfosfatemia/genética , Hipocalcemia/complicaciones , Hipoparatiroidismo/complicaciones , Masculino , Hormona Paratiroidea/deficiencia , Fenotipo , Neumonía Bacteriana/complicaciones , Tomografía Computarizada por Rayos X , Ácido Valproico/uso terapéuticoRESUMEN
Twenty-five dicentric small supernumerary marker chromosomes (sSMC) derived from #13/21, #14, #15, #18, and #22 were studied by immunohistochemistry for their centromeric activity. Centromere protein (CENP)-B was applied as marker for all centromeres and CENP-C to label the active ones. Three different 'predominant' activation patterns could be observed, i.e., centric fusion or either only one or all two centromeres were active. In one inherited case, the same activation pattern was found in mother and son. In acrocentric-derived sSMC, all three activation patterns could be present. In contrary, in chromosome 18-derived sSMC, only the fusion type was observed. In concordance with previous studies a certain centromeric plasticity was observed in up to 13% of the cells of an individual case. Surprisingly, the obtained data suggests a possible influence of the sSMC carrier's gender on the implementation of the predominant activation pattern; especially, only one active centromere was found more frequently in female than in male carriers. Also, it might be suggested that dicentric sSMC with one active centromere could be less stable than such with two active ones-centromeric plasticity might have an influence here, as well. Also, centromere activity in acrocentric-derived dicentrics could be influenced by heteromorphisms of the corresponding short arms. Finally, evidence is provided that the closer the centromeres of a dicentric are and if they are not fused, the more likely it was that both of them became active. In concordance and refinement with previous studies, a distance of 1.4 Mb up to about 13 Mb the two active centromere state was favored, while centromeric distance of over approximately 15 Mb lead to inactivation of one centromere. Overall, here, the first and largest ever undertaken study in dicentric sSMC is presented, providing evidence that the centromeric activation pattern is, and parental origin may be of interest for their biology. Influence of mechanisms similar or identical to meiotic imprinting in the centromeric regions of human chromosomes might be present. Furthermore, centromeric activation pattern could be at least in parts meaningful for the clinical outcome of dicentric sSMC, as sSMC stability and mosaicism can make the difference between clinically normal and abnormal phenotypes.
Asunto(s)
Centrómero/fisiología , Aberraciones Cromosómicas , Cromosomas Humanos , Cromosomas Humanos Par 13/ultraestructura , Cromosomas Humanos Par 14/ultraestructura , Cromosomas Humanos Par 15/ultraestructura , Cromosomas Humanos Par 18/ultraestructura , Cromosomas Humanos Par 22/ultraestructura , Femenino , Humanos , MasculinoRESUMEN
Thymic hypoplasia is a frequent feature of the 22q11.2 deletion syndrome, but we know little about patients' age-related thymic output and long-term consequences for their immune system. We measured the expression of T cell receptor rearrangement excision circles (TREC) and used flow cytometry for direct subtyping of recent thymic emigrant (RTE)-related T cells in 43 patients (aged 1-54 years; median 9 years) from all over Norway and in age-matched healthy controls. Thymic volumes were estimated by ultrasound in patients. TREC levels correlated well with RTE-related T cells defined by co-expression of CD3, CD45RA and CCR9 (r=0.84) as well as with the CD4+ and CD8+ T cell subtypes. RTE-related T cell counts also paralleled age-related TREC reductions. CD45RA+ T cells correlated well with absolute counts of CD4+ (r=0.87) and CD8+ (r=0.75) RTE-related T cells. Apart from CD45RA- T cells, all T cell subsets were lower in patients than in controls. Thymic volumes correlated better with RTE-related cells (r=0.46) than with TREC levels (r=0.38). RTE-related T cells and TREC levels also correlated well (r=0.88) in patients without an identifiable thymus. Production of RTEs is impaired in patients with a 22q11.2 deletion, and CCR9 appears to be a good marker for RTE-related T cells.
Asunto(s)
Deleción Cromosómica , Trastornos de los Cromosomas/inmunología , Cromosomas Humanos Par 22/ultraestructura , ADN Circular/sangre , Síndrome de DiGeorge/inmunología , Reordenamiento Génico de Linfocito T , Antígenos Comunes de Leucocito/análisis , Receptores CCR/análisis , Subgrupos de Linfocitos T/patología , Timo/patología , Adolescente , Adulto , Biomarcadores , Estudios de Casos y Controles , Niño , Preescolar , Trastornos de los Cromosomas/genética , Trastornos de los Cromosomas/patología , Cromosomas Humanos Par 22/genética , Síndrome de DiGeorge/genética , Síndrome de DiGeorge/patología , Femenino , Humanos , Lactante , Recuento de Linfocitos , Masculino , Persona de Mediana Edad , Tamaño de los Órganos , Subgrupos de Linfocitos T/química , Subgrupos de Linfocitos T/inmunología , Adulto JovenRESUMEN
The 22q11.2 deletion syndrome is a common genetic condition with an estimated prevalence between 1:2000 and 1:6000 live births in the US. The syndrome is manifested in multiple different craniofacial features. The nasal area is known to play a role in assessing the extent of dysmorphology of an individual patient. In this paper, we present a method for detecting and assessing the severity of a common nasal feature: the bulbous nasal tip. Our method locates the nose and computes four descriptors, each of which leads to a severity score. Experiments with the four severity scores and a combinations of the best two show that using all five scores gives the best prediction of bulbous nasal tip. Furthermore, the bulbous nasal tip measures outperformed the median of human experts and attains similar results to our own prior work on global descriptors [12] for prediction of 22q11.2DS.
Asunto(s)
Cromosomas Humanos Par 22/ultraestructura , Mutación , Nariz/anomalías , Reconocimiento de Normas Patrones Automatizadas , Adolescente , Adulto , Algoritmos , Automatización , Niño , Preescolar , Deleción Cromosómica , Femenino , Humanos , Imagenología Tridimensional , Lactante , Masculino , Cartílagos NasalesRESUMEN
PURPOSE: Desmoplastic small round cell tumor (DSRCT) is a rare, highly aggressive malignancy with distinctive histologic and immunohistochemical features occurring in a young population with a male predominance. The tumor appears to arise as masses in the abdominal cavity without a clear visceral origin. Five patients with DSRCT were treated as usual with combined chemoradiation and surgery. In addition, in our center, patients underwent autologous bone marrow transplant (BMT), which is a novel approach to this disease. METHODS: Charts of 5 patients (4 males, mean age of 11 years) treated between 2000 and 2007 were reviewed. The diagnosis of DSRCT was made on the basis of clinical examination, computed tomographic scan, and explorative laparotomy with biopsy, and biochemical markers were negative. All patients were treated with aggressive chemoradiation and surgery. Three patients also had autologous BMT. RESULTS: Three patients (BMT recipients) responded to treatment. The responding patients had surgery with the intent of removing all disease. Two patients died of their cancer, neither of whom underwent BMT. CONCLUSION: The patients DSRCT are sensitive to an aggressive combination of chemotherapy, surgical debulking, and radiation therapy, followed by autologous BMT. It appears that this new multifaceted treatment offers good palliation, which may prolong survival and a possible cure.
Asunto(s)
Neoplasias Abdominales/terapia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Trasplante de Médula Ósea , Neoplasias Pélvicas/terapia , Radioterapia Adyuvante , Sarcoma de Células Pequeñas/terapia , Neoplasias Abdominales/tratamiento farmacológico , Neoplasias Abdominales/genética , Neoplasias Abdominales/radioterapia , Neoplasias Abdominales/cirugía , Carboplatino/administración & dosificación , Niño , Cromosomas Humanos Par 11/genética , Cromosomas Humanos Par 11/ultraestructura , Cromosomas Humanos Par 22/genética , Cromosomas Humanos Par 22/ultraestructura , Terapia Combinada , Doxorrubicina/administración & dosificación , Etopósido/administración & dosificación , Femenino , Humanos , Ifosfamida/administración & dosificación , Neoplasias Hepáticas/tratamiento farmacológico , Neoplasias Hepáticas/secundario , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/secundario , Masculino , Terapia Neoadyuvante , Proteínas de Fusión Oncogénica/genética , Neoplasias Pélvicas/tratamiento farmacológico , Neoplasias Pélvicas/genética , Neoplasias Pélvicas/radioterapia , Neoplasias Pélvicas/cirugía , Sarcoma de Células Pequeñas/tratamiento farmacológico , Sarcoma de Células Pequeñas/genética , Sarcoma de Células Pequeñas/radioterapia , Sarcoma de Células Pequeñas/secundario , Sarcoma de Células Pequeñas/cirugía , Neoplasias del Bazo/tratamiento farmacológico , Neoplasias del Bazo/secundario , Translocación Genética , Trasplante Autólogo , Vincristina/administración & dosificaciónRESUMEN
We present a 23-year-old man with chronic neutrophilic leukemia (CNL). Physical examination revealed hepatosplenomegaly. Leukocytosis was evident with predominance of mature neutrophils with basophilic granules. Bone marrow aspiration revealed mature myeloid hyperplasia. Congenital Robertsonian translocation [45,XY,der(13;22)(q10;q10), in all of analyzed 20 cells] was detected; however, cytogenetic and molecular studies for 9:22 translocation were negative. He was diagnosed with CNL and hydroxyurea was started to control his symptoms and white blood cell count. He was then successfully treated with allogeneic bone marrow transplantation (BMT). Although the prognosis of CNL was not determined, curative therapy including allogeneic hematopoietic stem cell transplantation should be attempted in young patients with CNL.
Asunto(s)
Trasplante de Médula Ósea , Trastornos de los Cromosomas/genética , Cromosomas Humanos Par 13/ultraestructura , Cromosomas Humanos Par 22/ultraestructura , Leucemia Neutrofílica Crónica/cirugía , Translocación Genética , Transformación Celular Neoplásica/genética , Cromosomas Humanos Par 13/genética , Cromosomas Humanos Par 22/genética , Terapia Combinada , Citotoxinas/uso terapéutico , Humanos , Hidroxiurea/uso terapéutico , Cariotipificación , Leucemia Neutrofílica Crónica/tratamiento farmacológico , Leucemia Neutrofílica Crónica/genética , Masculino , Inducción de Remisión , Acondicionamiento Pretrasplante , Trasplante Homólogo , Adulto JovenRESUMEN
Chronic myelogenous leukemia (CML) is genetically characterized by the reciprocal translocation of chromosome 9 and 22. Around 5-8% of CML develop complex variant Ph translocations involving one or more chromosomal regions besides 9 and 22. Chromosome 3 is not frequently involved in complex translocations in CML. We report in this study a case of CML displaying a t(3;9;22) 3-way translocation. A review of the literature appears to indicate that CML patients with this translocation tend to have an aggressive course and poor outcome. Additional 3-way chromosome translocations associated with CML are also reviewed.
Asunto(s)
Cromosomas Humanos Par 22/ultraestructura , Cromosomas Humanos Par 3/ultraestructura , Cromosomas Humanos Par 9/ultraestructura , Leucemia Mieloide de Fase Crónica/genética , Translocación Genética , Anticuerpos Monoclonales/administración & dosificación , Anticuerpos Monoclonales de Origen Murino , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Benzamidas , Crisis Blástica/genética , Cromosomas Humanos Par 22/genética , Cromosomas Humanos Par 3/genética , Cromosomas Humanos Par 9/genética , Ciclofosfamida/administración & dosificación , Dasatinib , Dexametasona/administración & dosificación , Progresión de la Enfermedad , Doxorrubicina/administración & dosificación , Resistencia a Antineoplásicos , Resultado Fatal , Humanos , Mesilato de Imatinib , Cariotipificación , Leucemia Mieloide de Fase Crónica/tratamiento farmacológico , Leucemia Mieloide de Fase Crónica/patología , Masculino , Metotrexato/administración & dosificación , Persona de Mediana Edad , Cromosoma Filadelfia , Piperazinas/administración & dosificación , Piperazinas/farmacología , Pronóstico , Inhibidores de Proteínas Quinasas/administración & dosificación , Pirimidinas/administración & dosificación , Pirimidinas/farmacología , Rituximab , Tiazoles/administración & dosificación , Vincristina/administración & dosificaciónRESUMEN
Peripheral primitive neuroectodermal tumors - also known as Ewing sarcomas - are a rare type of malignant tumor the histology of which characteristically reveals the presence of small round cells. Typically, t(11;22) translocation is observed. We describe the case of a 45-year-old man with a subcutaneous peripheral primitive neuroectodermal tumor in which the t(11;22) translocation was detected. He was satisfactorily treated with surgery and radiotherapy.
Asunto(s)
Tumores Neuroectodérmicos Periféricos Primitivos/diagnóstico , Proteínas de Fusión Oncogénica/genética , Proteína Proto-Oncogénica c-fli-1/genética , Neoplasias de los Tejidos Blandos/diagnóstico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Biomarcadores de Tumor , Cromosomas Humanos Par 11/genética , Cromosomas Humanos Par 11/ultraestructura , Cromosomas Humanos Par 22/genética , Cromosomas Humanos Par 22/ultraestructura , Terapia Combinada , Ciclofosfamida/administración & dosificación , Doxorrubicina/administración & dosificación , Factor Estimulante de Colonias de Granulocitos/administración & dosificación , Humanos , Masculino , Persona de Mediana Edad , Proteínas de Neoplasias/análisis , Tumores Neuroectodérmicos Periféricos Primitivos/tratamiento farmacológico , Tumores Neuroectodérmicos Periféricos Primitivos/genética , Tumores Neuroectodérmicos Periféricos Primitivos/patología , Tumores Neuroectodérmicos Periféricos Primitivos/radioterapia , Tumores Neuroectodérmicos Periféricos Primitivos/cirugía , Proteína EWS de Unión a ARN , Sarcoma de Ewing/genética , Sarcoma de Ewing/patología , Hombro , Neoplasias de los Tejidos Blandos/tratamiento farmacológico , Neoplasias de los Tejidos Blandos/genética , Neoplasias de los Tejidos Blandos/patología , Neoplasias de los Tejidos Blandos/radioterapia , Neoplasias de los Tejidos Blandos/cirugía , Tejido Subcutáneo , Translocación Genética , Vincristina/administración & dosificaciónAsunto(s)
Antimetabolitos Antineoplásicos/farmacocinética , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Metotrexato/farmacocinética , Piperazinas/farmacología , Leucemia-Linfoma Linfoblástico de Células Precursoras B/tratamiento farmacológico , Pirimidinas/farmacología , Antimetabolitos Antineoplásicos/administración & dosificación , Antimetabolitos Antineoplásicos/análisis , Benzamidas , Cromosomas Humanos Par 22/ultraestructura , Cromosomas Humanos Par 9/ultraestructura , Citarabina/administración & dosificación , Interacciones Farmacológicas , Edema/inducido químicamente , Edema/tratamiento farmacológico , Etopósido/administración & dosificación , Femenino , Humanos , Mesilato de Imatinib , Leucovorina/uso terapéutico , Metotrexato/administración & dosificación , Metotrexato/análisis , Persona de Mediana Edad , Piperazinas/administración & dosificación , Piperazinas/efectos adversos , Derrame Pleural Maligno/inducido químicamente , Derrame Pleural Maligno/química , Leucemia-Linfoma Linfoblástico de Células Precursoras B/metabolismo , Pirimidinas/administración & dosificación , Pirimidinas/efectos adversos , Inhibidores del Simportador de Cloruro Sódico y Cloruro Potásico/uso terapéutico , Translocación GenéticaRESUMEN
Dermatofibrosarcoma protuberans (DFSP) is a soft tissue neoplasm of intermediate malignancy that is initially localized to the skin from where it can invade deep structures (fat, fascia, muscle and bone). It is the most frequent fibrohistiocytic tumor, comprising approximately 1.8 % of all soft tissue sarcomas and 0.1 % of all cancers. It has an estimated incidence of 0.8-5 cases per one million persons per year. Treatment of localized disease consists in complete surgical excision of the lesion by conventional surgery with wide margins (>3 cm) or by micrographic Mohs surgery. Although the cases of metastatic DFSP do not reach 5 % of the total, almost all of them appear after previous local relapses. The prognosis for metastatic cases is very poor with a survival of less than 2 years following detection of metastatic disease. Patients with locally advanced DFSP are not candidates for an initial radical surgical therapy therefore neoadyuvant treatment is required prior to surgery in order to reduce tumor burden. In this regard, chemotherapy and radiotherapy have not been highly efficacious so it is necessary to consider new alternatives. The demonstration of the oncogenic power of the translocation COL1A1-PDGFB in DFSP has allowed the successful introduction of drug therapy with antagonists of the PDGFB receptor for metastatic or locally advanced cases.
Asunto(s)
Neoplasias Cutáneas/patología , Antígenos CD34/análisis , Antineoplásicos/uso terapéutico , Benzamidas , Biomarcadores de Tumor/análisis , Quimioterapia Adyuvante , Cromosomas Humanos Par 17/ultraestructura , Cromosomas Humanos Par 22/genética , Cromosomas Humanos Par 22/ultraestructura , Terapia Combinada , Dermatofibrosarcoma/química , Dermatofibrosarcoma/clasificación , Dermatofibrosarcoma/tratamiento farmacológico , Dermatofibrosarcoma/genética , Dermatofibrosarcoma/patología , Dermatofibrosarcoma/cirugía , Diseño de Fármacos , Humanos , Mesilato de Imatinib , Cirugía de Mohs , Terapia Neoadyuvante , Invasividad Neoplásica , Proteínas de Neoplasias/análisis , Proteínas de Neoplasias/genética , Recurrencia Local de Neoplasia , Proteínas de Fusión Oncogénica/análisis , Proteínas de Fusión Oncogénica/genética , Piperazinas/uso terapéutico , Pronóstico , Pirimidinas/uso terapéutico , Receptor beta de Factor de Crecimiento Derivado de Plaquetas/antagonistas & inhibidores , Cromosomas en Anillo , Sarcoma/química , Sarcoma/tratamiento farmacológico , Sarcoma/genética , Sarcoma/patología , Sarcoma/cirugía , Neoplasias Cutáneas/química , Neoplasias Cutáneas/tratamiento farmacológico , Neoplasias Cutáneas/genética , Neoplasias Cutáneas/cirugía , Translocación GenéticaRESUMEN
To study 3D nuclear distributions of epigenetic histone modifications such as H3(K9) acetylation, H3(K4) dimethylation, H3(K9) dimethylation, and H3(K27) trimethylation, and of histone methyltransferase Suv39H1, we used advanced image analysis methods, combined with Nipkow disk confocal microscopy. Total fluorescence intensity and distributions of fluorescently labelled proteins were analyzed in formaldehyde-fixed interphase nuclei. Our data showed reduced fluorescent signals of H3(K9) acetylation and H3(K4) dimethylation (di-me) at the nuclear periphery, while di-meH3(K9) was also abundant in chromatin regions closely associated with the nuclear envelope. Little overlapping (intermingling) was observed for di-meH3(K4) and H3(K27) trimethylation (tri-me), and for di-meH3(K9) and Suv39H1. The histone modifications studied were absent in the nucleolar compartment with the exception of H3(K9) dimethylation that was closely associated with perinucleolar regions which are formed by centromeres of acrocentric chromosomes. Using immunocytochemistry, no di-meH3(K4) but only dense di-meH3(K9) was found for the human acrocentric chromosomes 14 and 22. The active X chromosome was observed to be partially acetylated, while the inactive X was more condensed, located in a very peripheral part of the interphase nuclei, and lacked H3(K9) acetylation. Our results confirmed specific interphase patterns of histone modifications within the interphase nuclei as well as within their chromosome territories.
Asunto(s)
Núcleo Celular/metabolismo , Histonas/metabolismo , Interfase/fisiología , Acetilación , Algoritmos , Centrómero/ultraestructura , Cromosomas Humanos Par 14/genética , Cromosomas Humanos Par 14/ultraestructura , Cromosomas Humanos Par 22/genética , Cromosomas Humanos Par 22/ultraestructura , Cromosomas Humanos X/genética , Cromosomas Humanos X/ultraestructura , Fibroblastos/metabolismo , Humanos , Procesamiento de Imagen Asistido por Computador , Inmunohistoquímica , Hibridación Fluorescente in Situ , MetilaciónRESUMEN
A translocation t(1;22)(p13;q13) was detected in a child with T-cell acute lymphoblastic leukemia (T-ALL). FISH studies showed that the breakpoint was located in the 5' part of the interleukin-2 receptor beta chain (IL2RB) locus, but could only be located distal to 1p13.3 on the partner chromosome. This is the first case of the IL2RB locus rearrangement in T-ALL. The localization of the breakpoint suggests that the chromosomal translocation results in deregulation of IL2RB expression.
Asunto(s)
Cromosomas Humanos Par 1/genética , Cromosomas Humanos Par 22/genética , Subunidad beta del Receptor de Interleucina-2/genética , Leucemia-Linfoma de Células T del Adulto/genética , Proteínas de Neoplasias/genética , Translocación Genética , Niño , Cromosomas Humanos Par 1/ultraestructura , Cromosomas Humanos Par 22/ultraestructura , Femenino , Regulación Leucémica de la Expresión Génica , Humanos , Hibridación Fluorescente in Situ , Subunidad beta del Receptor de Interleucina-2/biosíntesis , Cariotipificación , Proteínas de Neoplasias/biosíntesisRESUMEN
The t(9;22)(q34;q11), generating the Philadelphia chromosome, is found in more than 90% of patients with chronic myelocytic leukemia (CML). Deletions adjacent to the translocation breakpoint on the derivative chromosome 9 have been described by several groups. These studies revealed two primary points: (1) genomic microdeletions were concomitant with the t(9;22) rearrangement; and (2) the location of the deleted sequence was centromeric to ABL and telomeric to BCR genes. We report on a detailed molecular cytogenetic characterization of chromosomal rearrangements in two CML patients bearing a complex variant t(9;22) and insertions of chromosome 22 sequences in 9q34. Our study shows that the location of the deleted sequences was downstream of the ABL gene and that genomic microdeletions were concomitant with the ins(9;22)(q34;q11q11) rearrangement.
Asunto(s)
Deleción Cromosómica , Cromosomas Humanos Par 9 , Leucemia Mielógena Crónica BCR-ABL Positiva/genética , Cromosoma Filadelfia , Adulto , Aberraciones Cromosómicas , Cromosomas Humanos Par 22/ultraestructura , Cromosomas Humanos Par 9/ultraestructura , Femenino , Proteínas de Fusión bcr-abl/genética , Genes abl , Humanos , Hibridación Fluorescente in Situ , Leucemia Mielógena Crónica BCR-ABL Positiva/diagnóstico , Masculino , Persona de Mediana Edad , Proteínas Proto-Oncogénicas c-bcr/genéticaRESUMEN
Extraskeletal Ewing sarcoma (EES) represents a rare soft tissue malignant neoplasm histologically similar to skeletal Ewing sarcoma. It occurs mainly in adolescents and young adults and commonly affects the paravertebral regions. The differential diagnosis includes other small, blue round cells tumors. The authors report a case of an EES involving the spinal epidural and paravertebral spaces in an adolescent boy. EES diagnosis was confirmed by features of histologic analysis and immunohistochemistry and by the presence of the t(11;22)(q24;q12) chromosomal translocation by reverse transcriptase-polymerase chain reaction.