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Diffuse Large B-Cell Lymphoma (DLBCL) is an aggressive but potentially curable disease. There exists significant heterogeneity in the underlying biology of the disease, as evidenced by distinct subtypes. These subtypes are prognostic and offer utility in treatment decisions, and thus require an assay with a rapid turnaround time. Prior to the development of the Nanostring LST assay, research tools demonstrated varying assay accuracy and it was often difficult to detect subtype differences.
The RUO version of the NanoString Lymphoma Subtyping Test (LST) determines the Cell-of-Origin (COO) molecular subtype of samples run on the RUO LST CodeSet. Samples are reported as one of the two molecular subtypes, Activated-B-Cell (ABC), Germinal Center-B-Cell (GCB), or Unclassified. The Linear Predictor Score (LPS) is also reported.
LST RUO Assay At Work
The LST Signature
The LST CodeSet contains probes for the 20 genes within the LST signature, 15 target genes and 5 reference genes.
The signature was originally identified by performing gene expression profiling of DLBCL samples using microarrays (Alizadeh et al, 2000). The gene expression profiles indicated two different stages of B-cells differentiation: germinal center (GCB) and activated B cell based (ABC) based on the cell of origin and distinct mechanisms of oncogenesis. This signature was later refined to 20 genes using the FFPE tissues on the nCounter Analysis system (Scott et al, 2014).
NanoString developed a multiplex gene expression assay on the nCounter Analysis System that can identify the cell of origin (COO) subtypes (ABC-type or GCB-type) of DLBCL: the 20-gene assay was trained using 51 FFPE biopsies; the locked assay was validated using an independent cohort of 68 FFPE biopsies. Comparisons were made with COO assignment using the original COO model on matched frozen tissue. A linear predictor score (LPS) calculated as the weighted sum of the 15 normalized target genes compared to pre-defined thresholds determine the DLBCL cell-of-origin subtype.
Customers interested in obtaining an LST subtype data analysis report must purchase the report separately.
The LST Data Analysis Report
The Lymphoma Subtyping Test is based on the Leukemia and Lymphoma Molecular Profiling Project, also known as the Lymph2Cx assay and provides cell-of-origin data for diffuse large B-cell lymphomas.
The LST report includes the Linear Predictor Score (LPS) and the DLBCL cell of origin subtype: germinal center B-cell like (GCB), activated B-cell like (ABC), or Unclassified.
Publications & Posters
Determining Cell-of-Origin Subtypes of Diffuse Large B-cell Lymphoma Using Gene Expression in FFPE Tissue
Cell-of-Origin Subtype Classification of Diffuse Large B-Cell Lymphoma Using the Lymph2Cx Assay Retains Relevance in the Context of BCL2 and MYC Expression Status
In 2000, gene expression profiling (GEP) studies discovered two distinct, predominant genetic profiles associated with either a germinal center B-cell (GCB) or activated B-cell (ABC) cell-of-origin (COO) contributing to the morphologically and clinically heterogeneous nature of diffuse large B-cell lymphoma (DLBCL) (Alizadeh et al NEJM 2000). Follow-up GEP and sequencing studies confirmed the validity of the COO subgroup classification.
Reliable subtype classification of diffuse large B-cell lymphoma samples from GELA LNH2003 trials using the Lymph2Cx gene expression assay
Incorporation of digital gene expression profiling for cell-of-origin determination (Lymph2Cx testing) into the routine work-up of diffuse large B cell lymphoma
Diffuse large B cell lymphomas (DLBCL) represent a clinically heterogeneous group of lymphomas that are classified together based on similarities in morphology and immunophenotype. Gene expression profiling further classifies DLBCL into distinct molecular subgroups based on cell-of-origin (COO), including germinal center B cell type, activated B cell type, and unclassified type.
ROBUST: A Phase III Study of Lenalidomide Plus R-CHOP Versus Placebo Plus R-CHOP in Previously Untreated Patients With ABC-Type Diffuse Large B-Cell Lymphoma
Patients with the activated B-cell-like (ABC) subtype of diffuse large B-cell lymphoma (DLBCL) historically showed inferior survival with standard rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP). Phase II studies demonstrated that adding the immunomodulatory agent lenalidomide to R-CHOP improved outcomes in ABC-type DLBCL.
Cell‐of‐origin determined by both gene expression profiling and immunohistochemistry is the strongest predictor of survival in patients with diffuse large B‐cell lymphoma
The tumor cells in diffuse large B-cell lymphomas (DLBCL) are considered to originate from germinal center derived B-cells (GCB) or activated B-cells (ABC). Gene expression profiling (GEP) is preferably used to determine the cell of origin (COO).
Development of the molecular diagnostic (MDx) DLBCL Lymphoma Subtyping Test (LST) on the nCounter Analysis System.
Background: Diffuse large B-cell lymphoma (DLBCL) is an aggressive non-Hodgkin’s lymphoma with two distinct molecular cell-of-origin (COO) subtypes known as germinal center B-cell (GCB) or activated B-cell (ABC). DLBCL subtypes have been reported to be prognostic and potentially predictive of treatment benefit, underscoring the need for a precise and accurate MDx test.
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