Amplification of 9p24.1 in diffuse large B-cell lymphoma identifies a unique subset of cases that resemble primary mediastinal large B-cell lymphoma

Yucai Wang, Kerstin Wenzl, Michelle K. Manske, Yan W. Asmann, Vivekananda Sarangi, Patricia T. Greipp, Jordan E. Krull, Keenan Hartert, Rong He, Andrew L. Feldman, Matthew J. Maurer, Susan L. Slager, Grzegorz S. Nowakowski, Thomas M. Habermann, Thomas E. Witzig, Brian K. Link, Stephen M. Ansell, James R. Cerhan, Anne J. Novak

Research output: Contribution to journalArticle

5 Scopus citations

Abstract

Copy number alterations (CNAs) of 9p24.1 occur frequently in Hodgkin lymphoma, primary mediastinal large B-cell lymphoma (PMBCL), primary central nervous system lymphoma, and primary testicular lymphoma, resulting in overexpression of PD-L1 and sensitivity to PD-1 blockade-based immunotherapy. While 9p24.1 CNA was also reported in diffuse large B-cell lymphoma (DLBCL), little is known about its molecular or clinical significance. In this study, we analyzed the prevalence of 9p24.1 CNA in newly diagnosed DLBCL and examined its association with PD-L1, PD-L2, and JAK2 expression, clinical characteristics, and outcome. We found that 10% of DLBCL cases had CNA of 9p24.1, with 6.5% gains, and 3.5% amplifications. Only the cases with a 9p24.1 amplification had high levels of PD-L1, PD-L2, and JAK2 expression. Gains or amplifications of 9p24.1 were associated with a younger age and the ABC/non-GCB subtype. Compared with DLBCL cases without 9p24.1 CNA, the cases with a 9p24.1 amplification had a trend of better event-free survival. Furthermore, the amplification cases had a gene expression and mutation profile similar to those of PMBCL. Our data suggest that amplification of 9p24.1 identifies a unique subset of DLBCL with clinical and molecular features resembling PMBCL that may be amenable to PD-1 blockade-based immunotherapy.

Original languageEnglish (US)
Article number73
JournalBlood cancer journal
Volume9
Issue number9
DOIs
StatePublished - Sep 1 2019

ASJC Scopus subject areas

  • Hematology
  • Oncology

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