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
Altmetric Score
MSK Authors
  1. Venkatraman Ennapadam Seshan
    279 Seshan
  2. Carol Portlock
    174 Portlock
  3. Craig Moskowitz
    366 Moskowitz
  4. Ariela Noy
    202 Noy
  5. Maria Lia Palomba
    118 Palomba
  6. Steven M Horwitz
    338 Horwitz
  7. Andrew D Zelenetz
    538 Zelenetz
  8. Ross Levine
    462 Levine
  9. Alison Moskowitz
    133 Moskowitz
  10. Paul Hamlin
    167 Hamlin
  11. Matthew J Matasar
    116 Matasar
  12. David J Straus
    203 Straus
  13. Anita Kumar
    50 Kumar
  14. Kristina M Knapp
    32 Knapp
  15. Connie Wing-Ching Lee
    39 Lee
  16. Anas Younes
    186 Younes
  17. Patrick Dale Hilden
    78 Hilden
  18. Ahmet Dogan
    160 Dogan
  19. Erel Joffe
    3 Joffe
  20. Matahi Wilfrid Serge Moarii
    6 Moarii