RESUMO
Trisomic cells in neoplasms may represent abnormal clones originated from a tissue-confined mosaicism, and arise therefore by a meiotic error. We report on a 16-month-old child with erythroleukaemia (AML-M6), whose marrow karyotype at onset was 48,XX,del(13)(q12q14),del(14)(q22q32),+21,+21. The parental origin of the supernumerary chromosomes 21 was investigated by comparing 10 polymorphic loci scattered along the whole chromosome on the patient's marrow and her parents' leukocytes. Three loci were informative for the presence of three alleles, two of which were of maternal origin; two further loci showed a maternal allele of higher intensity. Lymphocytes and skin fibroblasts showed a normal karyotype, and molecular analysis on leukocytes at remission, buccal smear and urinary sediment cells consistently showed only one maternal allele, whereas neonatal blood from Guthrie spot showed two maternal alleles as in the marrow. An accurate clinical re-evaluation confirmed a normal phenotype. Our results indicate that tetrasomy 21 arose from a marrow clone with trisomy 21 of meiotic origin. To the best of our knowledge, this is the first evidence that supernumerary chromosomes in neoplastic clones may in fact be present due to a meiotic error. This demonstrates that a tissue-confined constitutional mosaicism for a trisomy may indeed represent the first event in multistep carcinogenesis.
Assuntos
Cromossomos Humanos Par 21 , Leucemia Eritroblástica Aguda/genética , Meiose , Mosaicismo/genética , Trissomia , Alelos , Aneuploidia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Medula Óssea/patologia , Transplante de Medula Óssea , Pré-Escolar , Células Clonais/patologia , Terapia Combinada , Dermatoglifia , Síndrome de Down/genética , Feminino , Sangue Fetal/química , Sangue Fetal/citologia , Seguimentos , Humanos , Hibridização in Situ Fluorescente , Interfase , Cariotipagem , Leucemia Eritroblástica Aguda/tratamento farmacológico , Leucemia Eritroblástica Aguda/terapia , Repetições de Microssatélites , Modelos Genéticos , Não Disjunção GenéticaAssuntos
Carcinoma Papilar/diagnóstico , Doença de Hodgkin , Segunda Neoplasia Primária/diagnóstico , Neoplasias da Glândula Tireoide/diagnóstico , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma Papilar/genética , Carcinoma Papilar/patologia , Carcinoma Papilar/terapia , Quimioterapia Adjuvante , Criança , Aberrações Cromossômicas , Transtornos Cromossômicos , Ciclofosfamida/administração & dosagem , Diagnóstico Diferencial , Doxorrubicina/administração & dosagem , Doença de Hodgkin/tratamento farmacológico , Doença de Hodgkin/radioterapia , Humanos , Masculino , Segunda Neoplasia Primária/genética , Segunda Neoplasia Primária/patologia , Segunda Neoplasia Primária/terapia , Prednisona/administração & dosagem , Procarbazina/administração & dosagem , Neoplasias da Glândula Tireoide/genética , Neoplasias da Glândula Tireoide/patologia , Neoplasias da Glândula Tireoide/terapia , Vincristina/administração & dosagemRESUMO
A reciprocal translocation (9;11) is often found in acute myeloid leukemia (AML), mostly of the M5a type. We report a case of a child with AML, in whom t(9;11) was observed at diagnosis as the sole structural abnormality, together with trisomies 19 and 21. The diagnosis was AML evolving from a myelodysplastic syndrome (MDS), and the blast morphology was undifferentiated. Chemotherapy failed to induce morphological remission and the patient's condition soon worsened. A subclone appeared and expanded during the course of the disease, with an additional unbalanced translocation (1;17) leading to trisomy of the long arm of chromosome 17 (17q). The data available from the literature on acquired anomalies involving 17q and our observation led us to postulate a specific link between the gain of 17q and complete chemoresistance.
Assuntos
Cromossomos Humanos Par 17/genética , Cromossomos Humanos Par 21/genética , Leucemia Mieloide/genética , Trissomia/genética , Doença Aguda , Anemia Refratária com Excesso de Blastos/genética , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Pré-Escolar , Cromossomos Humanos Par 1/genética , Cromossomos Humanos Par 9/genética , Progressão da Doença , Evolução Fatal , Marcadores Genéticos , Humanos , Hibridização in Situ Fluorescente , Cariotipagem , Leucemia Mieloide/tratamento farmacológico , Masculino , PrognósticoAssuntos
Cromossomos Humanos Par 8 , Rearranjo Gênico , Lipoma/genética , Neoplasias Cutâneas/genética , Feminino , Humanos , LactenteRESUMO
Previous cytogenetic studies have demonstrated that the majority of lipoblastomas show rearrangements, in particular translocations and insertions, with breakpoints in 8q11-13. Here we present evidence for involvement of the developmentally regulated zink finger gene PLAG1 in these rearrangements. Northern blot and RT-PCR analyses revealed overexpression of PLAG1 in two lipoblastomas. Using immunohistochemistry, expression of the PLAG1 protein was also demonstrated in tissue sections from two lipoblastomas, one of which had a t(3;8)(q13.1;q12) translocation and the other a t(1;6)(q42;p22) translocation. Since no aberrant PLAG1 transcripts could be detected, it is likely that the gene may be activated by promoter swapping/substitution or alternatively by an as yet unknown mechanism. Our findings indicate that PLAG1 activation is a recurrent event in lipoblastomas and that PLAG1 is likely to be the target gene on chromosome 8 in these tumors.
Assuntos
Cromossomos Humanos Par 8/genética , Proteínas de Ligação a DNA/metabolismo , Lipoma/metabolismo , Translocação Genética/fisiologia , Linhagem Celular , Proteínas de Ligação a DNA/genética , Humanos , Lipoma/genética , RNA/metabolismoRESUMO
Recent studies have shown that structural abnormalities of chromosome 17 resulting in gain of material are the most frequent genetic changes in neuroblastoma. We have established a new neuroblastoma cell line from a patient whose disease had evolved from stage 4s to 4, without evidence of deletion of the short arm of chromosome 1 and MYCN amplification, which are considered the most typical genetic indicators of aggressive disease. The cytogenetic study allowed a full characterization of the chromosome changes, and revealed a complex translocation of chromosome 17 leading to a derivative marker which may be described as follows: der(11)t(11;17)(p15;q12)t(11;17) (q22;q12). This resulted in a gain of part of the long arms of chromosome 17, which was recently associated with poor prognosis.
Assuntos
Cromossomos Humanos Par 17 , Neuroblastoma/genética , Translocação Genética/genética , Células Tumorais Cultivadas/patologia , Animais , Imunofluorescência , Humanos , Hibridização in Situ Fluorescente , Recém-Nascido , Cariotipagem , Masculino , Camundongos , Camundongos Nus , Transplante de Neoplasias , Neuroblastoma/patologiaRESUMO
Lipoblastoma is a rare benign adipose tumor which, in all of the cases so far described, presents an involvement of chromosome 8 in the region 8q11-13. We hereby report the results of the second case of lipoblastoma studied by fluorescence in situ hybridization (FISH), in a 13-month-old boy. An abnormal karyotype 46,XY,t(7;8)(q31;q13) was found in 90% of the metaphases examined, in agreement with the previously reported observations. We suggest the region 8q11-13 may contain a relevant locus for lipoblastoma origin.
Assuntos
Cromossomos Humanos Par 7 , Cromossomos Humanos Par 8 , Lipoma/genética , Translocação Genética , Humanos , Hibridização in Situ Fluorescente , Lactente , Cariotipagem , Lipoma/patologia , MasculinoRESUMO
Congenital leukemia is a rare disease accounting for about 1% of all leukemias in childhood. While cases associated with Down's syndrome not infrequently show a spontaneous regression, such an event is very rare in non-Down cases and exceptional in those (among the latter) which present clonal cytogenetic alterations in the neoplastic cells. We present the case of a patient with congenital leukemia and an abnormal karyotype (limited to the neoplastic clone), in which an apparently spontaneous and prolonged remission occurred after a relapse.
Assuntos
Aberrações Cromossômicas/genética , Leucemia/genética , Regressão Neoplásica Espontânea , Medula Óssea/patologia , Transtornos Cromossômicos , Feminino , Humanos , Lactente , Cariotipagem , RecidivaRESUMO
Of 175 CML patients studied, 14 variants were found, seven of which are presently described. The breakpoints involved in the translocation, other than 9q34 and 22q11, are 3p21, 5q13, 6p21, 7q22, 10q22, and 11p13. Fragile sites were investigated in some of these patients. In two cases a coincidence between fragile site location and breakpoint of the third chromosome involved in Philadelphia formation was found. This observation suggests that the fragile sites can lead to Ph variants in patients developing CML.
Assuntos
Fragilidade Cromossômica , Leucemia Mieloide/genética , Cromossomo Filadélfia , Translocação Genética , Adulto , Idoso , Afidicolina , Bandeamento Cromossômico , Sítios Frágeis do Cromossomo , Diterpenos/farmacologia , Marcadores Genéticos , Humanos , Cariotipagem , Pessoa de Meia-IdadeRESUMO
The karyotypes of 33 Philadelphia-positive chronic myelogenous leukemia patients during the blastic phase are reported. Only three patients (9%) had a Philadelphia clone without further chromosomal aberrations, whereas, all the others had karyotype evolution. Aside from some nonrandom abnormalities (+8, i(17q), +Ph, +19) we found a higher frequency of clones with random structural rearrangements (13 cases, 39.4%) than previously reported. From a clinical point of view, however, the additional chromosomal (structural) abnormalities do not significantly influence the patients' survival.
Assuntos
Crise Blástica , Leucemia Mieloide/genética , Cromossomo Filadélfia , Translocação Genética , Adolescente , Adulto , Idoso , Marcadores Genéticos , Humanos , Cariotipagem , Leucemia Mieloide/patologia , Pessoa de Meia-IdadeRESUMO
Seven cases of acute nonlymphoblastic leukemia showing t(8;21)(q22;q22) at diagnosis are described. Involvement of a sex chromosome was found in all patients (in six cases as a loss, and in one as a Y duplication), thus, confirming the suggestion of a correlation between these two chromosomal abnormalities. The constitutional folic acid-sensitive fragile site fra(8)(q22) was not detected, in spite of careful analysis of over 300 metaphases of cells grown in folic acid-free medium. Morphologic diagnoses and clinical aspects are briefly discussed.
Assuntos
Cromossomos Humanos 21-22 e Y , Cromossomos Humanos 6-12 e X , Leucemia Mieloide Aguda/genética , Translocação Genética , Adulto , Idoso , Medula Óssea/patologia , Criança , Pré-Escolar , Feminino , Humanos , Cariotipagem , Leucemia Mieloide Aguda/patologia , Leucemia Mieloide Aguda/fisiopatologia , Masculino , Pessoa de Meia-Idade , Aberrações dos Cromossomos Sexuais/genéticaRESUMO
An isochromosome (17q) may be observed in myelo- and lymphoproliferative disorders, as well as in solid tumours and it is very frequent in Ph1-positive chronic myelocytic leukaemia (CML) during the blastic phase. A study on the mechanism of origin and on the centromeric function of the i(17q)s was performed by means of the C- and Cd-staining techniques in four CML patients. In all these cases, as well as in four others reported in the literature, the i(17q) is dicentric thus indicating that its origin is due to a break on the short arms followed by joining of the two chromatids containing the centromere. The Cd-technique indicates that one of the two centromeres is inactive: this result is consistent with the fact that the i(17q) in CML is a step in the clonal evolution towards the acute phase.