Development and application of a new immunophenotypic algorithm for molecular subtype classification of Diffuse Large B-Cell Lymphoma (DLBCL): Report from an International DLBCL Rituximab-CHOP Consortium Program Study
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ABSTRACT: We studied 498 de-novo adult DLBCL cases, which had been diagnosed between January 2002 and October 2009, as part of the International DLBCL Rituximab-CHOP Consortium Program Study We perform global gene expression profiling from formalin fixed paraffin embedded 498 DLBCL tissues RNA by SPIA mediated microarray detection and identified the distinct subgroups of the disease within DLBCL, known as germinal-center-B-cell-like (GCB), activated B-cell-like (ABC), and unclassified DLBCL (UC). RNA of 498 FFPET DLBCL patient samples were extracted, amplified using a novel RNA amplicfication method, Single Primer Isothermal Amplification (SPIA, NuGen Inc.), and hybridized to Affymetrix HG-U133 Plus 2.0 GeneChips. This dataset is the collaboration between The University of Texas at MD Anderson Cancer Center and Roche Molecular Systems, Inc.
Project description:We studied 498 de-novo adult DLBCL cases, which had been diagnosed between January 2002 and October 2009, as part of the International DLBCL Rituximab-CHOP Consortium Program Study We perform global gene expression profiling from formalin fixed paraffin embedded 498 DLBCL tissues RNA by SPIA mediated microarray detection and identified the distinct subgroups of the disease within DLBCL, known as germinal-center-B-cell-like (GCB), activated B-cell-like (ABC), and unclassified DLBCL (UC).
Project description:An International Multi-Center Study to Define the Clinical Utility of MicroarrayâBased Gene Expression Profiling in the Diagnosis and Sub-classification of Leukemia (MILE Study) Established in 2005, the MILE (Microarray Innovations in LEukemia) study research program included 11 participating centers in three continents. This cohort of n=1,152 samples represents data on the retrospective whole-genome analysis phase. This dataset is part of the MILE Study (Microarray Innovations In LEukemia) program, headed by the European Leukemia Network (ELN) and sponsored by Roche Molecular Systems, Inc. 1,152 blood or bone marrow samples of acute and chronic leukemia patients were hybridized to the Roche AmpliChip Leukemia Custom Microarray
Project description:An International Multi-Center Study to Define the Clinical Utility of Microarray–Based Gene Expression Profiling in the Diagnosis and Sub-classification of Leukemia (MILE Study) Established in 2005, the MILE (Microarray Innovations in LEukemia) study research program included 11 participating centers in three continents. This cohort of n=2,096 samples represents data on the retrospective whole-genome analysis phase. This dataset is part of the MILE Study (Microarray Innovations In LEukemia) program, headed by the European Leukemia Network (ELN) and sponsored by Roche Molecular Systems, Inc. 2096 blood or bone marrow samples of acute and chronic leukemia patients were hybridized to Affymetrix HG-U133 Plus 2.0 GeneChips.
Project description:Rapid proteotyping of 41 FFPE DLBCL tumor tissues with 2-3 biological replicates using pressure-cycling technology (PCT) and SWATH mass spectrometry.
Project description:This study performed an in-depth investigation of the immune-molecular profiles of an unique cohort of extranodal diffuse large B-cell lymphoma (DLBCL) of the bone, with single primary bone (PB-)DLBCL and multiple localizations (polyostotic-DLBCL). A similar DLBCL cohort with nodal localizations only and germinal center B-cell (GCB) phenotype (nodal-DLBCL-GCB) was used as comparator. With comprehensive genomic mutational and gene gene-expression profiling (GEP), in total 103 DLBCLS were analyzed. Both molecular techniques revealed a shared mutational genomic and gene-expression transcriptomic profile for PB-DLBCL (n=51) and polyostotic-DLBCL (n=18), justifying a collective analysis as bone-DLBCL. Differential incidences of EZH2, IRF8, and HIST1H1E, and MYC mutations/rearrangements (p<0.05) confirmed the distinct oncogenic evolution of bone-DLBCL and nodal-DLBCL-GCB (n=34). Bone-DLBCL primarily exhibited an intermediate/rich immune TME GEP signature (p≤<0.005), based on published gene sets. Further unsupervised clustering identified two distinct groups, establishing a notable ‘immune-rich’ cluster dominated by bone-DLBCL (754%, p=0.0062). This immune-rich cluster demonstrated superior survival (p=≤0.0263) compared to the ‘immune-low’ cluster, which consisted mostly of nodal-DLBCL-GCB cases (61%). Gene-set enrichment analysis illustrated variations in cell proliferation and immune systemreceptor pathways for the immune-rich cluster (p<0.001), indicating a crucial role for the tumor microenvironment (TME) in disease behavior and outcome. Further supported by deconvolution applications (CIBERSORTx and single-sample gene-set enrichment analysis), The immune-rich cluster highlighted highlighting an abundantmainly regulatory T cells in immune-rich and cell proliferation in immune-low. infiltrate of NK/T, Treg, TFH and follicular dendritic cells (p<0.001). Conclusively, PB-DLBCL and polyostotic-DLBCL shared similar TME features and immune-molecular profiles. This study delineates tThe distinct immune-rich TME profile of bone-DLBCL, which is associated with a superior survival. These findings suggest that bone-DLBCL patients with immune-rich GEP might benefit from less intensive polychemotherapies and this could further shape targeted immunomodulatory strategies.
Project description:Cross-species comparative gene expression profiling was performed to identify differentially expressed genes conserved in aggressive B lymphomas. Whole genome expression arrays from mouse B220+ splenic B cells (wild-type C57BL/6, B6) were compared to whole tumors (approximately >75% neoplastic cells) from B6.iMyc mice. Correspondingly, isolated human peripheral blood B cells were compared to human diffuse large B cell (DLBCL) whole tumors (approximately >75% neoplastic cells) DLBCL.
Project description:Genomic profiles of DLBCL (Diffuse Large B-cell Lymphoma) patients 20 DLBCL patients were selected for detection of genomic aberrations
Project description:Gene expression profiling based classification of DLBCL patients versus healthy donors provides insights on transcriptional regulation processes. Within the most represented pathways in DLBCL, we identified an innate immune response signature, as well as an anti-inflammatory response. On the other hand, a significant under-representation of pathways involved in T-cell activation was also revealed. Whole blood from 76 DLBCL patients and 87 healthy donors was collected into PAXgene Blood RNA tubes (Becton Dickinson BD Biosciences, San Jose, CA, USA) ensuring blood stabilization and stored at -80°C before RNA extraction. Total RNA, after globin mRNA depletion, was hybridized onto Affymetrix GeneChip® Human Exon 1.0 ST oligonucleotide arrays (Affymetrix, Santa Clara, CA, USA) according to manufacturerâs instructions.