RESUMO
A tumor cell line, HCC1937, was established from a primary breast carcinoma from a 24-year-old patient with a germ-line BRCA1 mutation. A corresponding B-lymphoblastoid cell line was established from the patient's peripheral blood lymphocytes. BRCA1 analysis revealed that the tumor cell line is homozygous for the BRCA1 5382insC mutation, whereas the patient's lymphocyte DNA is heterozygous for the same mutation, as are at least two other family members' lymphocyte DNA. The tumor cell line is marked by multiple additional genetic changes including a high degree of aneuploidy, an acquired mutation of TP53 with wild-type allele loss, an acquired homozygous deletion of the PTEN gene, and loss of heterozygosity at multiple loci known to be involved in the pathogenesis of breast cancer. Comparison of the primary tumor with the cell line revealed the same BRCA1 mutation and an identical pattern of allele loss at multiple loci, indicating that the cell line had maintained many of the properties of the original tumor. This breast tumor-derived cell line may provide a useful model system for the study of familial breast cancer pathogenesis and for elucidating BRCA1 function and localization.
Assuntos
Neoplasias da Mama/genética , Neoplasias da Mama/patologia , Genes BRCA1 , Mutação em Linhagem Germinativa , Heterozigoto , Células Tumorais Cultivadas , Adulto , Alelos , DNA de Neoplasias/genética , Éxons , Feminino , Humanos , Cariotipagem , Linhagem , Polimorfismo Conformacional de Fita SimplesRESUMO
A maternal complex chromosome rearrangement (CCR) involving chromosomes 2, 13, and 20 was ascertained in a normal female through the diagnosis of a deletion of 13q in her daughter. The child has mild clinical features and developmental delay consistent with proximal deletions of 13q that do not extend into band q32 and a del(13)(q12q14.1) that does not involve the retinoblastoma locus by FISH. Maternal studies by GTG banding and FISH showed a complex karyotype with bands 13q12.3-->13q12.1::20p13 translocated to 2p13 and bands 2pter-->2p13::13q12.3-->13q14.1 translocated into band 20p13. This would be the first report of an interstitial deletion of 13q inherited from a parental complex chromosome rearrangement.
Assuntos
Deleção Cromossômica , Cromossomos Humanos Par 13 , Cromossomos Humanos Par 20 , Cromossomos Humanos Par 2 , Translocação Genética , Feminino , Humanos , LactenteRESUMO
A balanced Robertsonian translocation 45,XY,t(15q15q) was detected in a patient with mental retardation, microcephaly, and hypertonia. Deletion of the 15q11q13 region was unlikely based on fluorescence in situ hybridization studies that revealed hybridization of appropriate DNA probes to both arms of the Robertsonian chromosome. Inheritance of alleles from 13 highly polymorphic DNA markers on chromosome 15 showed paternal uniparental isodisomy. The clinical, cytogenetic, and molecular results are consistent with a diagnosis of Angelman syndrome.
Assuntos
Síndrome de Angelman/genética , Cromossomos Humanos Par 15 , Translocação Genética , Pré-Escolar , Aberrações Cromossômicas , Humanos , Cariotipagem , Masculino , Repetições de MicrossatélitesRESUMO
We describe two de novo cases of extra r(8) confirmed by fluorescent in situ hybridization (FISH). Based on these two and eight additional cases of extra r(8) confirmed by FISH, the phenotype is better documented. One of our patients had minor facial anomalies, near-normal growth, and neurological development. She had a ring in each cell analyzed. The second had minor craniofacial anomalies and growth and mental retardation. He had a small or double-sized ring in each cell. The phenotype of these 10 cases ranges from almost normal in an adult with 10% mosaicism to variable degrees of minor anomalies, growth retardation, and mental retardation overlapping the mosaic +8 syndrome.
Assuntos
Cromossomos Humanos Par 8 , Cromossomos em Anel , Feminino , Humanos , Hibridização in Situ Fluorescente , Lactente , Masculino , Fenótipo , SíndromeRESUMO
We describe a family in which two siblings exhibited developmental delay, reduced muscle tone and mild muscle weakness. Cytogenetic evaluation demonstrated that both children had a tandem duplication of a small portion of the long arm of chromosome 10 [46,XX or XY,dir dup(10)(q24.2-->q24.3)], inherited from their clinically normal mother, who was found to be mosaic for the duplicated chromosome 10. Fluorescence in situ hybridization approaches, including total chromosome painting and the use of regional specific cosmid probes, were used to confirm the chromosome 10q origin of the duplicated material. This is the smallest confirmed duplication of this portion of chromosome 10 reported to date.
Assuntos
Aberrações Cromossômicas , Cromossomos Humanos Par 10 , Deficiências do Desenvolvimento/genética , Impressão Genômica , Criança , Pré-Escolar , Bandeamento Cromossômico , Mapeamento Cromossômico , Cosmídeos , Feminino , Humanos , Hibridização in Situ Fluorescente , Testes de Inteligência , Cariotipagem , Masculino , Mosaicismo , Mães , TrissomiaRESUMO
We describe clinical and chromosomal findings in two patients with del(4q). Patient 1, with interstitial deletion (4)(q21.1q25), had craniofacial and skeletal anomalies and died at 8 months of hydrocephalus. Patient 2, with interstitial deletion (4)(q25q27), had craniofacial and skeletal anomalies with congenital hypotonia and developmental delay. These patients shared certain manifestations with other del(4q) patients but did not have Rieger anomaly. Clinical variability among patients with interstitial deletions of 4q may be related to variable expression, variable deletion, or imprinting of genes within the 4q region.
Assuntos
Anormalidades Múltiplas/genética , Deleção Cromossômica , Cromossomos Humanos Par 4 , Osso e Ossos/anormalidades , Ossos Faciais/anormalidades , Feminino , Humanos , Lactente , Masculino , Fenótipo , SíndromeRESUMO
Astrocytomas contain nonrandom chromosomal abnormalities that recently have been correlated with shortened patient survival. Two frequently reported aberrations are trisomy 7 and monosomy 10. We assessed the numerical complement of chromosomes 7 and 10 in formalin-fixed, paraffin-embedded brain biopsy tissue from 28 diffuse astrocytomas by in situ hybridization using a nonfluorescent enzymatic detection system. Clinical follow-up of at least 5 years was available in 26 cases (93%). Monosomy 10 was identified in 7 cases (25%): astrocytoma, 1 case; anaplastic astrocytoma, 1 case; and glioblastoma, 5 cases. Trisomy 7 was identified in 11 cases (39%): astrocytoma, 5 cases; glioblastoma, 6 cases. Multivariate analysis revealed that monosomy 10 was the most statistically significant negative predictor of patient survival. Numerical chromosomal abnormalities are detectable in astrocytomas in archival tissue using interphase cytogenetics and nonfluorescent light microscopy. Although larger studies are required, our data suggest that potentially useful prognostic information may be obtained with this approach.
Assuntos
Astrocitoma/patologia , Neoplasias Encefálicas/patologia , Cromossomos Humanos Par 10/genética , Cromossomos Humanos Par 7/genética , Monossomia , Adulto , Idoso , Astrocitoma/genética , Neoplasias Encefálicas/genética , Aberrações Cromossômicas/genética , DNA de Neoplasias/análise , Feminino , Formaldeído , Humanos , Hibridização In Situ , Masculino , Pessoa de Meia-Idade , Inclusão em Parafina , Prognóstico , Análise de Sobrevida , TrissomiaRESUMO
We report three cases of meningioma. Case 1 had a dicentric chromosome number 22 resulting in partial monosomy for a portion of the q-arm, i.e., 46,XX,idic(22)(pter-->q11.2::q11.2-->pter) and 46,XX,psu dic(22)(pter-->q11.2::q11.2-->pter), which was the sole clonal abnormality. The origin of the dicentric chromosome from 22 was confirmed by in situ hybridization studies, using biotin-labeled alpha centromeric DNA probes for the acrocentric chromosomes. Case 2 had two distinct clonal abnormalities: deletion of 22q and monosomy of 22. Case 3 also had a deleted 22q.
Assuntos
Deleção Cromossômica , Cromossomos Humanos Par 22 , Meningioma/genética , Monossomia , Idoso , Neoplasias Encefálicas/genética , Centrômero , Sondas de DNA , Feminino , Neoplasias de Cabeça e Pescoço/genética , Humanos , Hibridização In Situ , Cariotipagem , Pessoa de Meia-Idade , Neoplasias da Medula Espinal/genéticaRESUMO
We describe a case of acute myeloblastic leukemia with a novel isochromosome 18, i(18)(p10), preceded by aplastic anemia for six months. The patient is a cotton grower chronically exposed to pesticides. The significance of this chromosomal abnormality is unknown. The possible relationship to the preceding history of aplastic anemia and occupational pesticide exposure is speculated on. The possible mechanism of the association of acute leukemia and aplastic anemia is discussed.
Assuntos
Anemia Aplástica/patologia , Cromossomos Humanos Par 18/genética , Isocromossomos/genética , Leucemia Mieloide Aguda/genética , Pré-Leucemia/patologia , Doenças dos Trabalhadores Agrícolas/tratamento farmacológico , Doenças dos Trabalhadores Agrícolas/patologia , Anemia Aplástica/tratamento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Humanos , Cariotipagem , Leucemia Mieloide Aguda/tratamento farmacológico , Masculino , Pessoa de Meia-Idade , Exposição Ocupacional/efeitos adversos , Praguicidas/efeitos adversos , Pré-Leucemia/tratamento farmacológicoRESUMO
The most common cytogenetic abnormalities associated with myelodysplastic syndromes are deletions of chromosomes 5 and 7 and trisomy 8. Reciprocal translocation is relatively uncommon in refractory anemia. We describe a case of refractory anemia associated with trisomy 8 and a derivative chromosome 22 resulting from t(1;22)(q11;q11.2). The diseases and the role of the various genes that are mapped to these breakpoints are discussed. The prognostic significance of karyotypic abnormalities in refractory anemia are reviewed.
Assuntos
Anemia Refratária/genética , Cromossomos Humanos Par 1 , Cromossomos Humanos Par 22 , Translocação Genética , Idoso , Feminino , Humanos , Cariotipagem , PrognósticoRESUMO
The idiopathic hypereosinophilic syndromes (HES) are rare hematologic disorders characterized by persistent eosinophilia with organ involvement that encompass a wide spectrum of clinical and hematological disease states. We propose a classification scheme to further delineate these patients, and present a case of a 45-year-old male with persistent eosinophilia, severe tissue and hematologic involvement, and trisomy 15. Although multiple cytogenetic abnormalities have been associated with hypereosinophilic syndromes, this is the first reported case where trisomy 15 is the sole chromosomal abnormality.
Assuntos
Cromossomos Humanos Par 15/genética , Síndrome Hipereosinofílica/genética , Trissomia/genética , Adulto , Doença Crônica , Humanos , Síndrome Hipereosinofílica/classificação , Cariotipagem , MasculinoRESUMO
Double minute chromosomes (dmin) occur in about 3.3-10.6% of acute leukemia, especially in the elderly. However, dmins are relatively rare in myelodysplastic syndrome (MDS). We describe a case of refractory anemia with excess blasts associated with complex cytogenetic abnormalities, dmins, and brief survival.
Assuntos
Aberrações Cromossômicas/genética , Síndromes Mielodisplásicas/genética , Idoso , Aberrações Cromossômicas/patologia , Bandeamento Cromossômico , Transtornos Cromossômicos , Feminino , Amplificação de Genes , Humanos , Masculino , Pessoa de Meia-Idade , Síndromes Mielodisplásicas/patologiaRESUMO
Cytogenetic analysis of bone marrow cells was performed on a 2-year-old African-American male with Down syndrome (DS) and myelodysplastic syndrome (MDS), specifically refractory anemia with excess blasts in transformation (RAEB-T). Chromosome analysis showed, in addition to the constitutional trisomy 21, a trisomy of chromosome 11 and a dup(1)(q23q31). This duplication of 1q is apparently a new chromosomal abnormality in a child with MDS. Partial trisomy of the long arm of chromosome 1 has been reported by several authors and appears to represent a nonrandom chromosomal anomaly in patients with MDS/acute myelogenous leukemia and DS.
Assuntos
Anemia Refratária com Excesso de Blastos/genética , Aberrações Cromossômicas , Cromossomos Humanos Par 1 , Síndrome de Down/genética , Anemia Refratária com Excesso de Blastos/complicações , Anemia Refratária com Excesso de Blastos/tratamento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Pré-Escolar , Síndrome de Down/complicações , Humanos , Cariotipagem , Ativação Linfocitária , MasculinoRESUMO
We describe the first reported case of acute myelogenous leukemia with characteristics of megakaryoblastic differentiation and the t(15;17) chromosomal translocation, which has been associated with promyelocytic leukemia. The diagnostic, clinical, and therapeutic implications are discussed.
Assuntos
Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/patologia , Megacariócitos/patologia , Complicações Neoplásicas na Gravidez , Adolescente , Feminino , Humanos , Cariotipagem , Leucemia Megacarioblástica Aguda/patologia , Gravidez , Complicações Neoplásicas na Gravidez/patologiaRESUMO
We describe a case of multiple myeloma with unusual manifestations consisting of cutaneous xanthomatosis, temporal arteritis, retinal vasculitis with a complex karyotype, and a "jumping translocation" involving 1q21. The literature of cytogenetic studies of multiple myeloma and of jumping translocation is reviewed.
Assuntos
Cromossomos Humanos Par 1 , Mieloma Múltiplo/genética , Translocação Genética , Idoso , Feminino , Humanos , CariotipagemRESUMO
A renal cell carcinoma from a 15-year-old male had a 49,Y,t(X;1)(p11.2;q21), +der(X)t(X;1) (p11.2;q21), +5, -16, +17, +18 karyotype. This is the third report of a translocation involving a breakpoint at Xp11.2 in a renal cell carcinoma in a child. A total of nine cases of renal cell carcinoma involving Xp11, including this case, have been reported. Of the eight cases for which there are genetics reports, all are male. Patients with renal cell carcinoma with abnormalities at Xp11 appear to be younger than renal cell carcinoma patients overall.
Assuntos
Carcinoma de Células Renais/genética , Cromossomos Humanos Par 1 , Neoplasias Renais/genética , Translocação Genética/genética , Cromossomo X , Adolescente , Carcinoma de Células Renais/patologia , Aberrações Cromossômicas/genética , Humanos , Cariotipagem , Neoplasias Renais/patologia , MasculinoRESUMO
Metastatic fibrolamellar hepatocellular carcinoma (HCC) was detected in the abdominal lymph nodes of an adolescent male after resection of the primary tumor. No dividing cells were isolated from attempted cytogenetic studies of the primary tumor. However, cytogenetic analysis of lymph node metastases detected 9 and 12 months after partial hepatectomy revealed abnormal hypertriploid karyotypes, with a suggestion of clonal evolution: 62-92 < 3n >,XX, -Y, +3, +6, +6, +7, +7, +8, +10, +13, +15, +16, +20, -21, -22, +mar1 x 2, +mar[cp6]/46,XY[8] and 78 < 3n >,XX, -Y,der(1)t(1;1)(p36.1;q21), +4, +6, +6, +7, +7,i(8)(q10), +10, +15, +20, -21, -22, +mar1 x 2, +mar2[3]/46, XY[17], respectively. Karyotypes of this variant of HCC have not been reported previously. The cytogenetics of HCC are reviewed.
Assuntos
Carcinoma Hepatocelular/genética , Neoplasias Hepáticas/genética , Adolescente , Carcinoma Hepatocelular/patologia , Aberrações Cromossômicas/genética , Transtornos Cromossômicos , Humanos , Cariotipagem , Neoplasias Hepáticas/patologia , MasculinoRESUMO
Cytogenetic and fluorescence in situ hybridization (FISH) studies permit analyses of structural and numerical chromosome abnormalities. We compared modal chromosome count in cancer cells by FISH and classical cytogenetics (CC). Our cytogentic studies for chromosomes 3 and 17 on 134 human solid tumor cultures ¿57 small cell lung cancer (SCLC) and 77 non small cell lung cancers (NSCLC)¿, indicated a high incidence of numerical changes in these tumors. Using centromeric probes for chromosomes 3 and 17 we compared 15 tumor and 3 lymphoblastoid cultures, both by FISH (> 100 interphase nuclei) and by CC using trypsin-Giemsa G banding (> 20 metaphases). Although some intra-tumor heterogeneity was seen by FISH, we observed a high degree of concordancy (78%) in modal count by the two techniques.
Assuntos
Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma de Células Pequenas/genética , Aberrações Cromossômicas , Transtornos Cromossômicos , Cromossomos Humanos Par 17 , Cromossomos Humanos Par 3 , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Carcinoma Pulmonar de Células não Pequenas/patologia , Carcinoma de Células Pequenas/patologia , Linhagem Celular , Centrômero , Bandeamento Cromossômico/métodos , Citogenética/métodos , Humanos , Hibridização in Situ Fluorescente/métodos , Células Tumorais CultivadasRESUMO
Denovo deletions of 18p without other associated rearrangement are uncommon. For such a deletion to profoundly affect the fetus of a near normal phenotypic carrier would be rarer. We present such a case in which the chance of a cryptic rearrangement was ruled out by fluorescence in situ hybridization (FISH) analysis. Possible explanations for wide variations in clinical expression are discussed.
Assuntos
Deleção Cromossômica , Cromossomos Humanos Par 18 , Hibridização in Situ Fluorescente , Troca Materno-Fetal/genética , Adulto , Feminino , Humanos , Cariotipagem , Fenótipo , GravidezRESUMO
We present a case of a Caucasian multigravida with advanced maternal age who showed evidence of an unusual heterochromatin banding pattern on chromosome 9 and a similar fetal karyotype on amniocentesis. Although unusual banding patterns of this region have been described earlier, we report a new, clinically insignificant pattern. This case illustrates the care needed in analysing the heterochromatin region for accurate clinical interpretation of chromosome 9 polymorphisms.