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NanoString’s RUO Lymphoma Subtyping (LST) gene expression signature can be used to generate data for the determination of Cell-of-Origin (COO) molecular subtype of samples while simultaneously generating data to determine the Linear Predictor Score (LPS). The 20-gene LST signature measures gene expression to accurately determine Activated-B-Cell (ABC), Germinal Center-B-Cell (GCB), or Unclassified.
When used with the nCounter® platform, the signature has proven performance with RNA extracted from FFPE, fresh frozen or cell lines. The signature can be purchased in different product formats, including as a Custom CodeSet or as a Plus Product spike-in to any panel or Custom CodeSet.
LST RUO Assay At Work
The LST Signature
The Lymphoma Subtyping gene expression signature includes 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).
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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