RESUMO
BCL8 is a novel human gene family initially identified through cloning of BCL8A, located at the t(14;15)(q32;q11-q13) translocation breakpoint, in a case of diffuse large B-cell lymphoma. Multiple copies of BCL8A map to the 1-Mb proximal duplicated region at 15q. We identified additional copies on human chromosomes 13 (BCL8B), 22 (BCL8C), 2 (BCL8D), and 10 (BCL8E) by cDNA cloning and sequence analysis. BCL8A, BCL8C, BCL8D, and BCL8E are truncated at the genomic level and are presumably pseudogenes or sterile transcripts. BCL8B is expressed predominantly in human brain and encodes a 327-kDa protein with extensive homology to the Drosophila melanogaster protein kinase A anchoring protein RG. LRBA, a human gene with a ubiquitous expression pattern mapping to 4q32, encodes a protein closely related to BCL8. The phylogenetically conserved BCL8 gene family evolved by transchromosomal and intrachromosomal duplications within the human genome.
Assuntos
Proteínas Quinases Dependentes de AMP Cíclico/metabolismo , Família Multigênica , Proteínas de Neoplasias/genética , Proteínas Adaptadoras de Transdução de Sinal , Encéfalo/metabolismo , Proteínas de Transporte/genética , Sequência Conservada , Proteínas Quinases Dependentes de AMP Cíclico/genética , DNA Complementar , Evolução Molecular , Dosagem de Genes , Duplicação Gênica , Humanos , Hibridização in Situ Fluorescente , Análise de Sequência de DNARESUMO
To address the possible genetic relationship between primary mediastinal large-B-cell lymphoma (PMLBCL) and diffuse large-B-cell lymphoma (DLBCL), we compared DNA copy number changes identified by comparative genomic hybridization (CGH) analysis of 40 PMLBCL and 91 DLBCL tumors. We assessed their karyotypes by G-banding; amplification of MYC, BCL2, and REL genes by Southern blotting; and incidence of nonpolymorphic BCL6 mutations by single-strand conformation polymorphism analysis (SSCP). Overall, CGH identified overlapping and nonoverlapping patterns of DNA copy number changes in the two groups. Among the latter changes, gains of chromosomes 8, 11, 15, and 16 and losses of chromosomes 5, 10, 15, 16, 17, and 20 were seen only in DLBCL, and gains of chromosomes 10, 21, and 22 and losses of chromosomes 11, 13, and 18 were seen only in PMLBCL. Several overlapping changes were identified in both groups, with variation in incidence. Statistical analysis of these changes showed significant gains of chromosomes 3 (P Assuntos
Aberrações Cromossômicas
, Linfoma de Células B/genética
, Linfoma Difuso de Grandes Células B/genética
, Neoplasias do Mediastino/genética
, Adolescente
, Adulto
, Idoso
, Idoso de 80 Anos ou mais
, Bandeamento Cromossômico
, Proteínas de Ligação a DNA/biossíntese
, Proteínas de Ligação a DNA/genética
, Feminino
, Dosagem de Genes
, Rearranjo Gênico/genética
, Humanos
, Masculino
, Pessoa de Meia-Idade
, Mutação/genética
, Hibridização de Ácido Nucleico/métodos
, Polimorfismo Conformacional de Fita Simples
, Proteínas Proto-Oncogênicas/biossíntese
, Proteínas Proto-Oncogênicas/genética
, Proteínas Proto-Oncogênicas c-bcl-6
, Fatores de Transcrição/biossíntese
, Fatores de Transcrição/genética