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Gene expression profiles uncover molecular classifiers for the prediction of progression-free survival in diffuse large B-cell lymphoma: results of a DASL assay from formalin fixed paraffin embedded tissue

ABSTRACT: Diffuse large B-cell lymphoma (DLBCL) exhibits heterogeneous clinical outcomes even in tumors of the same stage and with similar pathological characteristics. A substantial number of patients with DLBCL still fail to be cured despite recent improvements in therapy. In this study, we used formalin fixed paraffin embedded (FFPE) tumor samples for microarray gene expression profiling to develop robust prognostic profiles for DLBCL.

ORGANISM(S): Homo sapiens

PROVIDER: GSE38202 | GEO | 2012/05/25

SECONDARY ACCESSION(S): PRJNA167518

REPOSITORIES: GEO

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Gene expression profiles uncover molecular classifiers for the prediction of progression-free survival in diffuse large B-cell lymphoma: results of a DASL assay from formalin fixed paraffin embedded tissue

Project description:Diffuse large B-cell lymphoma (DLBCL) exhibits heterogeneous clinical outcomes even in tumors of the same stage and with similar pathological characteristics. A substantial number of patients with DLBCL still fail to be cured despite recent improvements in therapy. In this study, we used formalin fixed paraffin embedded (FFPE) tumor samples for microarray gene expression profiling to develop robust prognostic profiles for DLBCL. We performed a retrospective microarray gene expression profiling study of FFPE from a cohort of DLBCL patients using the whole genome cDNA mediated Annealing, Selection and Ligation (WG-DASL) assay. After removing poor-quality samples, data from 164 patients were used for statistical analyses to develop and validate a prognostic gene expression signature using a gradient lasso and leave-one-out cross-validation process.

2012-05-24 | E-GEOD-38202 | biostudies-arrayexpress

Gene Expression Profiling of Formalin Fixed Paraffin Embedded Familial Breast Tumours Using the Whole Genome-DASL Assay

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Gene Expression Profiling of Formalin Fixed Paraffin Embedded Familial Breast Tumours Using the Whole Genome-DASL Assay

Project description:Tissue sample acquisition is a limiting step in many studies. There are many thousands of formalin fixed paraffin embedded archival blocks collected around the world, but in contrast relatively few fresh frozen samples in tumor banks. Once samples are fixed in formalin the RNA is degraded and traditional methods for gene expression profiling are not suitable. In this study we have evaluated the whole genome DASL assay from Illumina to perform transcriptomic analysis from archived breast tumor tissue fixed in formalin paraffin embedded blocks. We profiled 76 familial breast tumors from cases carrying a BRCA1, BRCA2 or ATM mutation, or from non-BRCA1/2 families. We found that replicate samples correlated well with each other (r2=0.9-0.98). In 12/15 cases, the matched formalin-fixed and frozen samples predicted the same tumor molecular subtypes with confidence. These results demonstrate that the whole genome DASL assay is a valuable tool to profile degraded RNA from archival FFPE material. This assay will enable transcriptomic analysis of a large number of archival samples that are stored in pathology archives around the globe and consequently will have the potential to improve our understanding and characterisation of many diseases.

2010-06-09 | GSE21921 | GEO

Cell-of-Origin Subtyping Diffuse Large B-Cell Lymphoma (DLCBL) by Using a 32-Gene Expression Assay in Formalin-Fixed Paraffin-Embedded Tissues

Project description:Objection: To evaluate a qPCR-based 32-gene expression assay to determine the cell-of-origin (COO) of diffuse large B-cell lymphoma (DLBCL) with formalin-fixed paraffin-embedded (FFPE) tissue. Methods: The most established subtyping algorithm, the COO model, categorizes DLBCL into activated B-cell (ABC) and germinal center B-cell (GCB)-like subgroups through gene expression profiling. Biopsy of DLBCL patients with paired FFPE and fresh frozen tissue were collected to assign COO based on the immunohistochemistry (IHC) algorithm (Han’s algorithm), qPCR-based 32-gene expression assay (DLBCL-COO assay) and global gene expression profiling with RNA-seq. Results: The DLBCL-COO assay demonstrated a significantly superior concordance of COO determination with the “gold standard” RNA-seq, comparing with the IHC assignment with Han’s algorithm (91.9% versus 77.5%; P = 0.005). Furthermore, overall survival of GCB patients defined by DLBCL-COO assay was superior significantly towards the ABC patients (Figure 2B, P = 0.023). This effect was not seen when tumors were classified by IHC algorithm. Conclusions: The DLBCL-COO assay provides flexibility and accuracy in DLBCL subtype characterization. These subtype distinctions should help guiding prognostic and therapeutic options for the patients in our daily practice.

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