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 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 Matthew Habermann, Thomas Elmer Witzig, Brian K. Link, Stephen Maxted Ansell, James R Cerhan, Anne J Novak

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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

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Lymphoma, Large B-Cell, Diffuse
B-Cell Lymphoma
Immunotherapy
Lymphoma
Hodgkin Disease
Transcriptome
Disease-Free Survival
Central Nervous System
Mutation

ASJC Scopus subject areas

  • Hematology
  • Oncology

Cite this

@article{141f16c868c44428a05a243e8652d3f7,
title = "Amplification of 9p24.1 in diffuse large B-cell lymphoma identifies a unique subset of cases that resemble primary mediastinal large B-cell lymphoma",
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.",
author = "Yucai Wang and Kerstin Wenzl and Manske, {Michelle K.} and Yan Asmann and Vivekananda Sarangi and Greipp, {Patricia T} and Krull, {Jordan E.} and Keenan Hartert and Rong He and Feldman, {Andrew L} and Maurer, {Matthew J.} and Slager, {Susan L} and Nowakowski, {Grzegorz S} and Habermann, {Thomas Matthew} and Witzig, {Thomas Elmer} and Link, {Brian K.} and Ansell, {Stephen Maxted} and Cerhan, {James R} and Novak, {Anne J}",
year = "2019",
month = "9",
day = "1",
doi = "10.1038/s41408-019-0233-5",
language = "English (US)",
volume = "9",
journal = "Blood Cancer Journal",
issn = "2044-5385",
publisher = "Nature Publishing Group",
number = "9",

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TY - JOUR

T1 - Amplification of 9p24.1 in diffuse large B-cell lymphoma identifies a unique subset of cases that resemble primary mediastinal large B-cell lymphoma

AU - Wang, Yucai

AU - Wenzl, Kerstin

AU - Manske, Michelle K.

AU - Asmann, Yan

AU - Sarangi, Vivekananda

AU - Greipp, Patricia T

AU - Krull, Jordan E.

AU - Hartert, Keenan

AU - He, Rong

AU - Feldman, Andrew L

AU - Maurer, Matthew J.

AU - Slager, Susan L

AU - Nowakowski, Grzegorz S

AU - Habermann, Thomas Matthew

AU - Witzig, Thomas Elmer

AU - Link, Brian K.

AU - Ansell, Stephen Maxted

AU - Cerhan, James R

AU - Novak, Anne J

PY - 2019/9/1

Y1 - 2019/9/1

N2 - 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.

AB - 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.

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