RESUMO
We present a patient with stage III de novo diffuse large B-cell lymphoma. The lymphoma cells showed mature B-cell immunophenotype but lacked surface immunoglobulin (Ig) expression. Long-distance and long-distance inverse polymerase chain reaction assays to detect the oncogene/Ig gene rearrangement revealed that the cells carried 3 independent fusion genes, namely, c-MYC/Ig heavy chain gene (IgH), BCL2/IgH, and Ig lambda light chain gene/BCL6. Thus, the lymphoma cells concurrently carried t(8;14)(q24;q32), t(14;18)(q32;q21), and t(3;22)(q27;q11), which developed in association with class switching, V/D/J recombination, and somatic hypermutation, respectively. The lymphoma responded to chemoradiotherapy, and the patient has been well for 2 years, suggesting that multiple oncogene rearrangements may not necessarily be associated with poor clinical outcome.
Assuntos
Cromossomos Humanos/ultraestrutura , Proteínas de Ligação a DNA/genética , Genes bcl-2 , Genes myc , Linfoma de Células B/genética , Linfoma Difuso de Grandes Células B/genética , Proteínas Proto-Oncogênicas/genética , Proto-Oncogenes , Fatores de Transcrição/genética , Translocação Genética , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carboplatina/administração & dosagem , Cromossomos Humanos/genética , Cromossomos Humanos Par 14/genética , Cromossomos Humanos Par 14/ultraestrutura , Cromossomos Humanos Par 18/genética , Cromossomos Humanos Par 18/ultraestrutura , Cromossomos Humanos Par 22/genética , Cromossomos Humanos Par 22/ultraestrutura , Cromossomos Humanos Par 3/genética , Cromossomos Humanos Par 3/ultraestrutura , Cromossomos Humanos Par 8/genética , Cromossomos Humanos Par 8/ultraestrutura , Terapia Combinada , Dexametasona/administração & dosagem , Etoposídeo/administração & dosagem , Humanos , Ifosfamida/administração & dosagem , Linfoma de Células B/tratamento farmacológico , Linfoma de Células B/radioterapia , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Linfoma Difuso de Grandes Células B/radioterapia , Masculino , Pessoa de Meia-Idade , Proteínas Proto-Oncogênicas c-bcl-6 , Radioterapia Adjuvante , Indução de RemissãoRESUMO
We report the case of a 27-year old woman who presented hypocalcemia and hyperphosphoremia during her first pregnancy. Her phenotype was in favor of Albright's hereditary osteodystrophy: short stature, obesity, round face, brachymetacarpy and mental retardation. However, the diagnosis of pseudohypopara thyroidism type Ia was ruled out due to low PTH level (10 pg/ml). The patient's 22q11 microdeletion was suspected and identified because of the association of severe neonatal hypocalcemia, abnormal face and renal malformation in her children. Deletion 22q11 leads to various syndromes, including Di George syndrome, also referred to as CATCH 22 syndrome (Cardiac defect (C), Abnormal face (A), Thymic hypoplasia (T), Cleft palate (C) and Hypocalcemia (H)). Retrospectively, the patient presented with symptoms suggestive of CATCH 22: abnormal face, hypernasal voice suggestive of velopharyngeal insufficiency, mental retardation, recurrent otitis in childhood. It is also noteworthy that there was an idiopathic thrombocytopenic purpura. In conclusion, while the phenotype was suggestive of Albright's hereditary osteodystrophy, the constatation of a low PTH level would cast doubt on this diagnosis. Furthermore, the 22q11 microdeletion should be searched by FISH (Fluorescence In Situ Hybridization) in all patients with hypopara thyroidism of unknown origin, even in the absence of cardiac malformations. Finally, it seems that patients with CATCH 22 would be predisposed to auto-immune disease as a result of thymic dysfunction.
Assuntos
Deleção Cromossômica , Transtornos Cromossômicos/diagnóstico , Cromossomos Humanos Par 22/ultraestrutura , Hipercalcemia/etiologia , Hipoparatireoidismo/diagnóstico , Fósforo/sangue , Complicações na Gravidez/diagnóstico , Pseudo-Hipoparatireoidismo/diagnóstico , Anormalidades Múltiplas/genética , Adulto , Transtornos Cromossômicos/genética , Transtornos Cromossômicos/patologia , Diagnóstico Diferencial , Face/anormalidades , Feminino , Displasia Fibrosa Poliostótica/diagnóstico , Humanos , Hipercalcemia/congênito , Hipoparatireoidismo/genética , Hibridização in Situ Fluorescente , Recém-Nascido , Deficiência Intelectual/etiologia , Obesidade/etiologia , Hormônio Paratireóideo/deficiência , Fenótipo , Gravidez , Complicações na Gravidez/metabolismo , Púrpura Trombocitopênica Idiopática/complicações , Escoliose/etiologia , Síndrome , Insuficiência Velofaríngea/etiologiaRESUMO
DiGeorge syndrome is a human developmental disorder resulting in hypoplasia of the thymus and parathyroids, and conotruncal heart defects. We recently isolated four genes with zinc finger DNA binding motifs mapping to chromosome 22q11.2 DiGeorge critical region. We now report that one of them, ZNF74 gene, is hemizygously deleted in 23 out of 24 DiGeorge syndrome patients tested. ZNF74 mRNA transcripts are detected in human and mouse embryos but not in adult tissues. Sequence analysis of a corresponding cDNA reveals an an open reading frame encoding 12 zinc finger motifs of the Kruppel/TFIIIA type as well as N-terminal and C-terminal non-zinc finger domains. These results suggest that changes in the dosage of a putative transcription factor through ZNF74 hemizygous deletion may be critical for DiGeorge developmental anomalies.