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

• Published in: Blood cancer journal (New York) Vol. 9; no. 9; pp. 73 - 11
• Main Authors: Wang, Yucai, Wenzl, Kerstin, Manske, Michelle K., Asmann, Yan W., Sarangi, Vivekananda, Greipp, Patricia T., Krull, Jordan E., Hartert, Keenan, He, Rong, Feldman, Andrew L., Maurer, Matthew J., Slager, Susan L., Nowakowski, Grzegorz S., Habermann, Thomas M., Witzig, Thomas E., Link, Brian K., Ansell, Stephen M., Cerhan, James R., Novak, Anne J.
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 30.08.2019; Springer Nature B.V
• Subjects: 631/67/1990/291/1621/1915; 631/67/68; Biomedical and Life Sciences; Biomedicine; Cancer Research; Cell Line, Tumor; DNA Copy Number Variations - genetics; Female; Gene expression; Gene Expression Profiling - methods; Hematology; Humans; Immunotherapy; Lymphoma; Lymphoma, Large B-Cell, Diffuse - genetics; Male; Oncology
• ISSN: 2044-5385; 2044-5385
• DOI: 10.1038/s41408-019-0233-5

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.