Double-hit Signature with TP53 Abnormalities Predicts Poor Survival in Patients with Germinal Center Type Diffuse Large B-cell Lymphoma Treated with R-CHOP
- 7 January 2021
- journal article
- research article
- Published by American Association for Cancer Research (AACR) in Clinical Cancer Research
- Vol. 27 (6), 1671-1680
- https://doi.org/10.1158/1078-0432.ccr-20-2378
Abstract
Purpose: We performed detailed genomic analysis on 87 cases of de novo diffuse large B-cell lymphoma of germinal center type (GCB DLBCL) to identify characteristics that are associated with survival in those treated with R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone). Experimental Design: The cases were extensively characterized by combining the results of immunohistochemistry, cell-of-origin gene expression profiling (Nanostring), double-hit gene expression profiling (DLBCL90), fluorescence in situ hybridization (FISH) cytogenetic analysis for double/triple-hit lymphoma, copy number analysis (CNA), and targeted deep sequencing using a custom mutation panel of 334 genes. Results: We identified four distinct biologic subgroups with different survivals, and with similarities to the genomic classifications from two large retrospective studies of DLBCL. Patients with the double-hit signature but no abnormalities of TP53, and those lacking EZH2 mutation and/or BCL2 translocation, had an excellent prognosis. However, patients with an EZB-like profile had an intermediate prognosis, whereas those with TP53 inactivation combined with the double-hit signature had an extremely poor prognosis. This latter finding was validated using two independent cohorts. Conclusions: We propose a practical schema to utilize genomic variables to risk-stratify patients with GCB DLBCL. This schema provides a promising new approach to identify high-risk patients for new and innovative therapies.Keywords
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Funding Information
- NIH (P30CA033572)
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