T-Cell Lymphoma Clonality by Copy Number Variation Analysis of T-Cell Receptor Genes

Simple Summary T-cells defend the human body from pathogenic invasion via specific recognition by T-cell receptors (TCRs). The TCR genes undergo recombination (rearrangement) in a myriad of possible ways to generate different TCRs that can recognize a wide diversity of foreign antigens. However, in patients with T-cell lymphoma (TCL), a particular T-cell becomes malignant and proliferates, resulting in a population of genetically identical cells with same TCR rearrangement pattern. To help diagnose patients with TCL, a polymerase chain reaction (PCR)-based assay is currently used to determine if neoplastic cells in patient samples are of T-cell origin and bear identical (monoclonal) TCR rea…

Abstract PO-35: Prognostic significance of MYC, BCL2, and BCL6 colocalization at single-cell resolution in DLBCL

Abstract MYC, BCL2, and BCL6 are commonly used markers for immunohistochemistry of Diffuse large B-cell lymphomas (DLBCL). Coexpression of MYC and BCL2 in particular constitutes a subgroup of “double expressor lymphomas” (DEL) with a distinct poor clinical outcome. However, it is not known if MYC and BCL2/BCL6 coexpression occurs in the same cell or in different cells within the tumor, as traditional immunohistochemistry (IHC) is limited by the number of markers that can be simultaneously assessed within formalin-fixed, paraffin-embedded (FFPE) samples. We set out to discover the clinical significance of MYC, BCL2, and BCL6 colocalization at single-cell resolution using multiplexed quantita…

DIGITAL SPATIAL PROFILING OF DIFFUSE LARGE B‐CELL LYMPHOMAS REVEALS STING AS AN IMMUNE‐RELATED DETERMINANT OF SURVIVAL AFTER R‐CHOP THERAPY

Patterns of oncogene co-expression at single cell resolution in cancer influence survival

AbstractBackgroundCancers often overexpress multiple clinically relevant oncogenes. However, it is not known if multiple oncogenes within a cancer combine uniquely in specific cellular sub-populations to influence clinical outcome. We studied this phenomenon using the prognostically relevant oncogenes MYC, BCL2 and BCL6 in Diffuse Large B-Cell Lymphoma (DLBCL).MethodsQuantitative multispectral imaging simultaneously measured oncogene co-expression at single-cell resolution in reactive lymphoid tissue (n=12) and four independent cohorts (n=409) of DLBCL. Mathematically derived co-expression phenotypes were evaluated in DLBCLs with immunohistochemistry (n=316) and eight DLBCL cohorts with gen…

MYC, BCL2 AND BCL6 COEXPRESSION PATTERNS AT SINGLE‐CELL RESOLUTION RE‐DEFINE DOUBLE EXPRESSOR LYMPHOMAS

Immune pathway upregulation and lower genomic instability distinguish EBV-positive nodal T/NK-cell lymphoma from ENKTL and PTCL-NOS

Primary Epstein-Barr virus (EBV)-positive nodal T/NK-cell lymphoma (PTCL-EBV) is a poorly understood disease which shows features resembling extranodal NK/T-cell lymphoma (ENKTL) and is currently not recognized as a distinct entity but categorized as a variant of primary T-cell lymphoma not otherwise specified (PTCL-NOS). Herein, we analyzed copynumber aberrations (n=77) with a focus on global measures of genomic instability and homologous recombination deficiency and performed gene expression (n=84) and EBV miRNA expression (n=24) profiling as well as targeted mutational analysis (n=16) to further characterize PTCL-EBV in relation to ENKTL and PTCL-NOS. Multivariate analysis revealed that …