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1.
Blood ; 113(5): 1053-61, 2009 Jan 29.
Artigo em Inglês | MEDLINE | ID: mdl-18978208

RESUMO

Follicular lymphoma (FL) is a morphologically and genetically well-characterized B-cell non-Hodgkin lymphoma that can show predominantly follicular, combined follicular and diffuse, or predominantly diffuse growth patterns. Although approximately 85% of FLs harbor the translocation t(14;18)(q32;q21) and consistently display a follicular growth pattern, predominantly diffuse FLs are less well characterized on the phenotypical, molecular, and clinical level. We studied 35 predominantly diffuse FL by immunohistochemistry, classical chromosome banding analysis, fluorescence in situ hybridization (FISH), and gene expression profiling. A total of 28 of 29 analyzable cases lacked t(14;18), and 27 of 29 cases revealed a unifying chromosomal aberration, a deletion in 1p36. Morphologically, 12 FLs were grade 1 and 23 were grade 2, and the immunophenotype with frequent expression of CD10, BCL6, and CD23 was in line with a germinal center B-cell phenotype. The gene expression profiles of 4 predominantly diffuse FLs fell into the spectrum of typical FL, with a unique enrichment of specific gene signatures. Remarkably, patients with diffuse FL frequently presented with low clinical stage and large but localized inguinal tumors. These results suggest that predominantly diffuse FL represent a distinct subtype of t(14;18)-negative nodal FL with a unifying genetic alteration (deletion of 1p36) and characteristic clinical features.


Assuntos
Biomarcadores Tumorais/biossíntese , Deleção Cromossômica , Regulação Leucêmica da Expressão Gênica , Linfoma de Células B/metabolismo , Linfoma de Células B/patologia , Linfoma Folicular/metabolismo , Linfoma Folicular/patologia , Proteínas de Neoplasias/biossíntese , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/genética , Cromossomos Humanos Par 14/genética , Cromossomos Humanos Par 18/genética , Feminino , Centro Germinativo/metabolismo , Centro Germinativo/patologia , Humanos , Linfoma de Células B/genética , Linfoma Folicular/genética , Masculino , Pessoa de Meia-Idade , Proteínas de Neoplasias/genética , Translocação Genética
2.
Br J Haematol ; 142(4): 538-50, 2008 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-18564361

RESUMO

Mantle cell lymphoma (MCL) is an aggressive lymphoid tumour characterized by the translocation t(11;14)(q13;q32) and a poor clinical outcome (median survival: 3-4 years). Recent studies revealed that increased proliferation of the tumour cells and certain chromosomal aberrations, such as deletions of 17p13 and 9p21 represent major adverse biological markers in this disease, although the molecular targets of chromosomal imbalances in MCL have not been identified for the large majority of loci affected. To correlate histomorphological and proliferation features of MCL with genetic findings, we investigated 223 MCL by fluorescence in situ hybridization (FISH) (n = 157) and/or classical cytogenetic banding analysis (n = 129). FISH analysis turned out to be distinctly more sensitive in the delineation of aberrations. Complex karyotypic alterations were associated with higher proliferation indices and inferior prognosis. A comprehensive analysis of biological features including genetic alterations in MCL by hierarchical clustering resulted in the delineation of four tumour subgroups differing with respect to their genetic constitution and suggesting different transformation or progression pathways. Moreover, in one of the groups identified, a more indolent clinical behaviour was associated with few secondary aberrations and fewer known high-risk chromosomal aberrations, which points to the importance of the quality of karyotypic evolution in MCL tumours.


Assuntos
Interfase/genética , Linfoma de Célula do Manto/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Antígenos CD/sangue , Biomarcadores Tumorais/sangue , Citogenética , Feminino , Humanos , Imuno-Histoquímica , Hibridização in Situ Fluorescente , Linfoma de Célula do Manto/imunologia , Linfoma de Célula do Manto/mortalidade , Masculino , Pessoa de Meia-Idade , Análise de Sobrevida , Translocação Genética , Proteína Supressora de Tumor p53/metabolismo
3.
J Hematop ; 1(2): 85-95, 2008 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-19669207

RESUMO

Mantle cell lymphomas (MCL), characterized by the t(11;14)(q13;q32), frequently carry secondary genetic alterations such as deletions in chromosome 17p involving the TP53 locus. Given that the association between TP53-deletions and concurrent mutations of the remaining allele is weak and based on our recent report that the Hypermethylated in Cancer 1 (HIC1) gene, that is located telomeric to the TP53 gene, may be targeted by deletions in 17p in diffuse large B-cell lymphoma (DLBCL), we investigated whether HIC1 inactivations might also occur in MCL. Monoallelic deletions of the TP53 locus were detected in 18 out of 59 MCL (31%), while overexpression of p53 protein occurred in only 8 out of 18 of these MCL (44%). In TP53-deleted MCL, the HIC1 gene locus was co-deleted in 11 out of 18 cases (61%). However, neither TP53 nor HIC1 deletions did affect survival of MCL patients. In most analyzed cases, no hypermethylation of the HIC1 exon 1A promoter was observed (17 out of 20, 85%). However, in MCL cell lines without HIC1-hypermethylation, the mRNA expression levels of HIC1 were nevertheless significantly reduced, when compared to reactive lymph node specimens, pointing to the occurrence of mechanisms other than epigenetic or genetic events for the inactivation of HIC1 in this entity.

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