4.7 Article

Double-hit Signature with TP53 Abnormalities Predicts Poor Survival in Patients with Germinal Center Type Diffuse Large B-cell Lymphoma Treated with R-CHOP

期刊

CLINICAL CANCER RESEARCH
卷 27, 期 6, 页码 1671-1680

出版社

AMER ASSOC CANCER RESEARCH
DOI: 10.1158/1078-0432.CCR-20-2378

关键词

-

类别

资金

  1. City of Hope National Medical Center Department of Pathology
  2. NCI of the NIH [P30CA033572]
  3. Toni Stephenson Lymphoma Center

向作者/读者索取更多资源

Detailed genomic analysis of 87 cases of GCB DLBCL identified four distinct biological subgroups with different survivals. A practical schema was proposed to risk-stratify patients with GCB DLBCL and to identify high-risk patients for new and innovative therapies.
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 IHC, cell-of-origin gene expression profiling (GEP; NanoString), double-hit GEP (DLBCL90), FISH cytogenetic analysis for double/triple-hit lymphoma, copy-number analysis, 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 use 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.

作者

我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。

评论

主要评分

4.7
评分不足

次要评分

新颖性
-
重要性
-
科学严谨性
-
评价这篇论文

推荐

暂无数据
暂无数据