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


Authors: Intlekofer, A. M.; Joffe, E.; Batlevi, C. L.; Hilden, P.; He, J.; Seshan, V. E.; Zelenetz, A. D.; Palomba, M. L.; Moskowitz, C. H.; Portlock, C.; Straus, D. J.; Noy, A.; Horwitz, S. M.; Gerecitano, J. F.; Moskowitz, A.; Hamlin, P.; Matasar, M. J.; Kumar, A.; van den Brink, M. R.; Knapp, K. M.; Pichardo, J. D.; Nahas, M. K.; Trabucco, S. E.; Mughal, T.; Copeland, A. R.; Papaemmanuil, E.; Moarii, M.; Levine, R. L.; Dogan, A.; Miller, V. A.; Younes, A.
Article Title: Integrated DNA/RNA targeted genomic profiling of diffuse large B-cell lymphoma using a clinical assay
Abstract: 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. © 2018 The Author(s).
Journal Title: Blood Cancer Journal
Volume: 8
Issue: 6
ISSN: 2044-5385
Publisher: Nature Publishing Group  
Date Published: 2018-06-12
Start Page: 60
Language: English
DOI: 10.1038/s41408-018-0089-0
PROVIDER: scopus
PMCID: PMC5997645
PUBMED: 29895903
DOI/URL:
Notes: Matahi Moarii's name is misspelled on the original publication -- Article -- Export Date: 2 July 2018 -- Source: Scopus
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MSK Authors
  1. Venkatraman Ennapadam Seshan
    285 Seshan
  2. Carol Portlock
    178 Portlock
  3. Craig Moskowitz
    371 Moskowitz
  4. Ariela Noy
    204 Noy
  5. Maria Lia Palomba
    121 Palomba
  6. Steven M Horwitz
    351 Horwitz
  7. Andrew D Zelenetz
    547 Zelenetz
  8. Ross Levine
    469 Levine
  9. Alison Moskowitz
    141 Moskowitz
  10. Paul Hamlin
    170 Hamlin
  11. Matthew J Matasar
    119 Matasar
  12. David J Straus
    205 Straus
  13. Anita Kumar
    51 Kumar
  14. Kristina M Knapp
    32 Knapp
  15. Connie Wing-Ching Lee
    42 Lee
  16. Anas Younes
    195 Younes
  17. Patrick Dale Hilden
    82 Hilden
  18. Ahmet Dogan
    166 Dogan
  19. Erel Joffe
    3 Joffe
  20. Matahi Wilfrid Serge Moarii
    6 Moarii