Project description:The survival of patients with diffuse large-B-cell lymphoma after chemotherapy is influenced by molecular features of the tumors. We used the gene-expression profiles of these lymphomas to develop a molecular predictor of survival. METHODS: Biopsy samples of diffuse large-B-cell lymphoma from 240 patients were examined for gene expression with the use of DNA microarrays and analyzed for genomic abnormalities. Subgroups with distinctive gene-expression profiles were defined on the basis of hierarchical clustering. A molecular predictor of risk was constructed with the use of genes with expression patterns that were associated with survival in a preliminary group of 160 patients and was then tested in a validation group of 80 patients. The accuracy of this predictor was compared with that of the international prognostic index. RESULTS: Three gene-expression subgroups--germinal-center B-cell-like, activated B-cell-like, and type 3 diffuse large-B-cell lymphoma--were identified. Two common oncogenic events in diffuse large-B-cell lymphoma, bcl-2 translocation and c-rel amplification, were detected only in the germinal-center B-cell-like subgroup. Patients in this subgroup had the highest five-year survival rate. To identify other molecular determinants of outcome, we searched for individual genes with expression patterns that correlated with survival in the preliminary group of patients. Most of these genes fell within four gene-expression signatures characteristic of germinal-center B cells, proliferating cells, reactive stromal and immune cells in the lymph node, or major-histocompatibility-complex class II complex. We used 17 genes to construct a predictor of overall survival after chemotherapy. This gene-based predictor and the international prognostic index were independent prognostic indicators.
Project description:Diffuse large B-cell lymphoma (DLBCL), the most common lymphoid malignancy in adults, is curable in less than 50% of patients. Prognostic models based on pre-treatment characteristics, such as the International Prognostic Index (IPI), are currently used to predict outcome in DLBCL. However, clinical outcome models identify neither the molecular basis of clinical heterogeneity, nor specific therapeutic targets. We analyzed the expression of 6,817 genes in diagnostic tumor specimens from DLBCL patients who received cyclophosphamide, adriamycin, vincristine and prednisone (CHOP)-based chemotherapy, and applied a supervised learning prediction method to identify cured versus fatal or refractory disease. The algorithm classified two categories of patients with very different five-year overall survival rates (70% versus 12%). The model also effectively delineated patients within specific IPI risk categories who were likely to be cured or to die of their disease. Genes implicated in DLBCL outcome included some that regulate responses to B-cell-receptor signaling, critical serine/threonine phosphorylation pathways and apoptosis. Our data indicate that supervised learning classification techniques can predict outcome in DLBCL and identify rational targets for intervention. golub-00095 Assay Type: Gene Expression Provider: Affymetrix Array Designs: Hu6800 Organism: Homo sapiens (ncbitax) Tissue Sites: Lymphoid tissue Material Types: synthetic_DNA, synthetic_RNA, organism_part Cell Types: B-Lymphocyte Disease States: Diffuse large B-cell Lymphoma, Follicular Lymphoma
Project description:Transformation of Follicular Lymphoma to Diffuse Large Cell Lymphoma: Alternative Patterns with Increased or Decreased Expression of c-myc and its Regulated genes The natural history of follicular lymphoma (FL) is frequently characterized by transformation to a more aggressive diffuse large B cell lymphoma (DLBCL). We compared the gene expression profiles between transformed DLBCL and their antecedent FL. No genes were observed to increase or decrease their expression in all the cases of histological transformation. However, two different gene expression profiles associated with the transformation process were defined, one in which c-myc and genes regulated by c-myc showed increased expression and one in which these same genes showed decreased expression. Further, there was a striking difference in gene expression profiles between transformed DLBCL and de novo DLBCL, since the gene expression profile of transformed DLBCL was more similar to their antecedent FL than to de novo DLBCL. The study demonstrates that transformation from FL to DLBCL can occur by alternative pathways and that transformed DLBCL and de novo DLBCL have very different gene expression profiles that may underlie the different clinical behaviors of these two types of morphologically similar lymphomas.
Project description:The aggressive B cell lymphoma diffuse large B cell lymphoma (DLBCL) is a heterogeneous entity that requires more precise monitoring and prognosis molecular tools. Extracellular vesicles that are secreted by all cell types are currently recognized as serving as a proxy for the cell of origin. Utilizing cutting-edge mass spectrometry, the current study described and assessed the plasma small extracellular vesicles (sEVs) proteome's diagnostic and prognostic potential. The presence of DLBCL has a significant impact on the sEV proteome, and several proteins substantially correlate with DLBCL.Nevertheless, no proteins that highly correlated with non-GCB or GCB were found.
Project description:This SuperSeries is composed of the following subset Series: GSE21846: Transcriptional profiling of 29 cases of diffuse large B cell lymphoma GSE21847: miRNA profiling of 29 cases of diffuse large B cell lymphoma GSE21848: miRNA profiling of 36 cases of diffuse large B cell lymphoma Refer to individual Series
Project description:Diffuse large B-cell lymphoma (DLBCL) is currently divided into three main molecular subtypes, defined by gene expression profiling (GEP): Germinal Center B-cell like (GCB), Activated B-Cell like (ABC), and Primary Mediastinal B-cell Lymphoma (PMBL). DLBCL subtypes were determined according to patients' gene expression profiles.
Project description:To understand the biological function of GSTT1 deletion in diffuse large B cell lymphoma (DLBCL), we identified genes that are expressed differently in lymph node tissues from DLBCL patients collected at diagnosis with GSTT1 deletion (4 cases) compared to those without GSTT1 deletion (4 cases).
Project description:Diffuse large B-cell lymphoma (DLBCL), the most common subtype of non-Hodgkin's lymphoma, is clinically heterogeneous: 40% of patients respond well to current therapy and have prolonged survival, whereas the remainder succumb to the disease. We proposed that this variability in natural history reflects unrecognized molecular heterogeneity in the tumors. Using DNA microarrays, we have conducted a systematic characterization of gene expression in B-cell malignancies. Here we show that there is diversity in gene expression among the tumors of DLBCL patients, apparently reflecting the variation in tumor proliferation rate, host response and differentiation state of the tumor. We identified two molecularly distinct forms of DLBCL which had gene expression patterns indicative of different stages of B-cell differentiation. One type expressed genes characteristic of germinal center B cells ('germinal center B-like DLBCL'); the second type expressed genes normally induced during in vitro activation of peripheral blood B cells ('activated B-like DLBCL'). Patients with germinal center B-like DLBCL had a significantly better overall survival than those with activated B-like DLBCL. The molecular classification of tumors on the basis of gene expression can thus identify previously undetected and clinically significant subtypes of cancer. This study is described more fully in Alizadeh AA et al.(2000) Nature 403:503-11
Project description:We performed a veterinary clinical oncology trial in client-owned dogs to determine if immune modulating drugs could be combined in rational approaches to treat spontaneous canine diffuse large B cell lymphoma (DLBCL).