Integrated DNA/RNA targeted genomic profiling of diffuse large B-cell lymphoma using a clinical assay

Andrew M. Intlekofer, Erel Joffe, Connie L. Batlevi, Patrick Hilden, Jie He, Venkatraman E. Seshan, Andrew D. Zelenetz, M. Lia Palomba, Craig H. Moskowitz, Carol Portlock, David J. Straus, Ariela Noy, Steven M. Horwitz, John F. Gerecitano, Alison Moskowitz, Paul Hamlin, Matthew J. Matasar, Anita Kumar, Marcel R. Van Den Brink, Kristina M. KnappJanine D. Pichardo, Michelle K. Nahas, Sally E. Trabucco, Tariq Mughal, Amanda R. Copeland, Elli Papaemmanuil, Mathai Moarii, Ross L. Levine, Ahmet Dogan, Vincent A. Miller, Anas Younes

Research output: Contribution to journalArticlepeer-review


We sought to define the genomic landscape of diffuse large B-cell lymphoma (DLBCL) by using formalin-fixed paraffin-embedded (FFPE) biopsy specimens. We used targeted sequencing of genes altered in hematologic malignancies, including DNA coding sequence for 405 genes, noncoding sequence for 31 genes, and RNA coding sequence for 265 genes (FoundationOne-Heme). Short variants, rearrangements, and copy number alterations were determined. We studied 198 samples (114 de novo, 58 previously treated, and 26 large-cell transformation from follicular lymphoma). Median number of GAs per case was 6, with 97% of patients harboring at least one alteration. Recurrent GAs were detected in genes with established roles in DLBCL pathogenesis (e.g. MYD88, CREBBP, CD79B, EZH2), as well as notable differences compared to prior studies such as inactivating mutations in TET2 (5%). Less common GAs identified potential targets for approved or investigational therapies, including BRAF, CD274 (PD-L1), IDH2, and JAK1/2. TP53 mutations were more frequently observed in relapsed/refractory DLBCL, and predicted for lack of response to first-line chemotherapy, identifying a subset of patients that could be prioritized for novel therapies. Overall, 90% (n = 169) of the patients harbored a GA which could be explored for therapeutic intervention, with 54% (n = 107) harboring more than one putative target.

Original languageEnglish
Article number60
JournalBlood Cancer Journal
Issue number6
StatePublished - 1 Jun 2018
Externally publishedYes


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