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Cited by 35Lymphoma Diagnosis and TreatmentChronic Lymphocytic Leukemia ResearchCNS Lymphoma Diagnosis and Treatment

The DOI matches its Crossref record; 3 of the 3 references it cites were found in a registry or an index.

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

Open access
Intlekofer, Andrew M., Joffe, Erel, Batlevi, Connie L., Hilden, Patrick, He, Jie, Seshan, Venkatraman E., Zelenetz, Andrew D., Palomba, M. Lia, Moskowitz, Craig H., Portlock, Carol, Straus, David J., Noy, Ariela, Horwitz, Steven M., Gerecitano, John F., Moskowitz, Alison, Hamlin, Paul, Matasar, Matthew J, Kumar, Anita, van den Brink, Marcel R., Knapp, Kristina M., Pichardo, Janine D., Nahas, Michelle K., Trabucco, Sally E., Mughal, Tariq, Copeland, Amanda R., Papaemmanuil, Elli, Moarii, Mathai, Levine, Ross L., Dogan, Ahmet, Miller, Vincent A., Younes, Anas·2018·Blood Cancer Journal
DOI 10.1038/s41408-018-0089-0PMC PMC5997645
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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.

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  • NRF2-activating mutations have been associated with chemo- and radiation resistance in lymphoma, leukemia, and solid tumors.

    “NRF2-activating mutations are rare in untreated lymphomas; however, they have been associated with chemo- and radiation resistance in lymphoma [37,38], leukemia [39], and in solid tumors [40].”

    From NRF2 Activation Confers Resistance to eIF4A Inhibitors in Cancer Therapy (2021) · cites this paper as [37]

    The citation is attached to the lymphoma portion of the resistance claim. The Results and Discussion passages in our copy discuss other genomic alterations in diffuse large B-cell lymphoma, but do not address NRF2-activating mutations or their association with chemotherapy or radiation resistance; searches for NRF2, NFE2L2, KEAP1, and treatment resistance found no relevant passage. The leukemia and solid-tumor portions are attributed to other citations. (LLM, conf=0.74)

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Research works printed but not linked: 24

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Metadata

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.
Affiliations
  • Memorial Sloan Kettering Cancer Center (US)
  • Foundation Medicine (United States) (US)
Corresponding author
Younes, Anas
ORCID
Venue
Blood Cancer Journal
Publisher
Springer Science and Business Media LLC
Published
2018-06-12
Volume
8
Issue
6
Pages
60-60
ISSN
2044-5385 (ISSN-L)
DOI
10.1038/s41408-018-0089-0
PMC
PMC5997645
OpenAlex
W2808005169
Cited by
35
References
3
Citations by year
2026: 1 · 2025: 3 · 2024: 5 · 2023: 3 · 2022: 4 · 2021: 7 · 2020: 6 · 2019: 6
FWCI
3.61
Type
journal article
Language
en
Open access
Licence
Locations
  • Blood Cancer Journal (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, other-oa)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
Funders
  • Memorial Sloan-Kettering Cancer Center (CA008748, P30 CA008748, Support Grant NIH P30 CA008748, NIH P30CA008748)
  • National Institutes of Health (CA008748, NIH P30 CA008748)
  • Foundation Medicine
  • National Cancer Institute (NIH P30 CA008748, CA192937, CA008748, P50CA192937, K08CA201483, P30CA008748)
Topics
  • Health Sciences › Medicine › Pathology and Forensic Medicine › Lymphoma Diagnosis and Treatment
  • Health Sciences › Medicine › Hematology › Chronic Lymphocytic Leukemia Research
  • Health Sciences › Medicine › Clinical Neurology › CNS Lymphoma Diagnosis and Treatment
Keywords
diffuse large B-cell lymphoma, genetic alterations, formalin-fixed paraffin-embedded tissue, MyD88, CREB-binding protein, CD79b, EZH2, TET2, TP53 mutation, relapsed/refractory lymphoma, therapeutic target, BRAF, PD-L1, IDH2, JAK1/2, copy number alterations, gene rearrangement
MeSH terms
Aged, Aged, 80 and over, Antineoplastic Combined Chemotherapy Protocols, Biopsy, Female, Humans, Male, Middle Aged, Neoplasm Staging, Prognosis, Biomarkers, Tumor, Lymphoma, Large B-Cell, Diffuse, Treatment Outcome, Computational Biology, Gene Expression Profiling, Genomics, DNA Copy Number Variations, Molecular Sequence Annotation, High-Throughput Nucleotide Sequencing, Transcriptome, Neoplasm Grading

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