Diffuse large B cell lymphoma (DLBCL) is an aggressive form of B-cell non Hodgkin lymphoma (NHL) and the most common type of NHL. With its heterogeneous nature in clinical behavior, morphology and immunophenotype, reliable biomarkers are needed to accurately categorize the tumor subtypes. Recent advancement in gene expression profiling has defined clinically important predictive biomarkers based on “cell-of-origin” (COO), which categorizes DLBCL into 2 specific subtypes with distinct mutational patterns and clinical outcome. MYC and BCL2 translocations are other genomic characteristics which are used as an additional prognostic tool to further characterize the COO subtypes to determine prognosis for DLBCL patients. Recently, the team led by Dr. Scott has revealed the location of MYC rearrangement at base pair resolution by performing targeted sequencing of MYC, BCL2, BCL6 and IG loci. The team discovered a novel recurrent MYC partner, RFTN1, and identified clinically relevant architecture of MYC rearrangement in DLBCL (Chong et al., Blood Advances, 2018). To further dissect the subtypes of DLBCL, RNA sequencing, targeted sequencing and whole-exome sequencing data from 157 de novo GCB-DLBCLs were analyzed, and a new clinically relevant assay was developed based on 104-gene double-hit signatures (DHITsig). Our data showed that DHITsig positive patients have inferior outcomes compared to DHITsig negative patients. The new assay, DLBCL90, identifies a clinically and biologically distinct group within GCB-DLBCL characterized by a gene expression signature of high-grade B-cell lymphoma with double/triple hit (HGBL-DH/TH-BCL2) and helps guide clinical management of this aggressive disease (Ennishi et al., J. Clin. Oncol, 2018). The aim of this program is to improve patient outcomes by comprehensively characterizing the aggressive B-cell lymphoma subtypes and developing clinically relevant assays.
Lymphoma/Leukemia Molecular Profiling Project (LLMPP Program)
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