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1000 Titel
  • Molecularly Stratified Treatment Options in Primary Refractory DLBCL/HGBL with MYC and BCL2 or BCL6 Rearrangements (HGBL, NOS with MYC/BCL6)
1000 Autor/in
  1. WITTE, HANNO |
  2. Riedl, Jörg |
  3. Künstner, Axel |
  4. Fähnrich, Anke |
  5. Ketzer, Julius |
  6. Fliedner, Stephanie M. J. |
  7. Reimer, Niklas |
  8. Bernard, Veronica |
  9. von Bubnoff, Nikolas |
  10. Merz, Hartmut |
  11. Busch, Hauke |
  12. Feller, Alfred |
  13. Gebauer, Niklas |
1000 Verlag
  • Springer International Publishing
1000 Erscheinungsjahr 2023
1000 Publikationstyp
  1. Artikel |
1000 Online veröffentlicht
  • 2023-07-24
1000 Erschienen in
1000 Quellenangabe
  • 18(5):749-765
1000 Copyrightjahr
  • 2023
1000 Lizenz
1000 Verlagsversion
  • https://doi.org/10.1007/s11523-023-00983-5 |
  • https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10517902/ |
1000 Publikationsstatus
1000 Begutachtungsstatus
1000 Sprache der Publikation
1000 Abstract/Summary
  • Background!#!There is growing evidence supporting multidisciplinary molecular tumor boards (MTB) in solid tumors whereas hematologic malignancies remain underrepresented in this regard.!##!Objective!#!The present study aimed to assess the clinical relevance of MTBs in primary refractory diffuse large B-cell lymphomas/high-grade B-cell lymphomas with MYC and BCL2 rearrangements (prDLBCL/HGBL-MYC/BCL2) (n = 13) and HGBL, not otherwise specified (NOS), with MYC and BCL6 rearrangements (prHGBL, NOS-MYC/BCL6) (n = 6) based on our previously published whole-exome sequencing (WES) cohort.!##!Patients and methods!#!For genomic analysis, the institutional MTB WES pipeline (University Cancer Center Schleswig-Holstein: UCCSH), certified for routine clinical diagnostics, was employed and supplemented by a comprehensive immunohistochemical work-up. Consecutive database research and annotation according to established evidence levels for molecularly stratified therapies was performed (NCT-DKTK/ESCAT).!##!Results!#!Molecularly tailored treatment options with NCT-DKTK evidence level of at least m2A were identified in each case. We classified mutations in accordance with biomarker/treatment baskets and detected a heterogeneous spectrum of targetable alterations affecting immune evasion (IE; n = 30), B-cell targets (BCT; n = 26), DNA damage repair (DDR; n = 20), tyrosine kinases (TK; n = 13), cell cycle (CC; n = 7), PI3K-MTOR-AKT pathway (PAM; n = 2), RAF-MEK-ERK cascade (RME; n = 1), and others (OTH; n = 11).!##!Conclusion!#!Our virtual MTB approach identified potential molecularly targeted treatment options alongside targetable genomic signatures for both prDLBCL/HGBL-MYC/BCL2 and prHGBL, NOS-MYC/BCL6. These results underline the potential of MTB consultations in difficult-to-treat lymphomas early in the treatment sequence.
1000 Sacherschließung
lokal Proto-Oncogene Proteins c-bcl-6/genetics [MeSH]
lokal Medical and Health Sciences
lokal Lymphoma, Large B-Cell, Diffuse/genetics [MeSH]
lokal Lymphoma, Large B-Cell, Diffuse/drug therapy [MeSH]
lokal Proto-Oncogene Proteins c-myc/genetics [MeSH]
lokal B-Lymphocytes [MeSH]
lokal Humans [MeSH]
lokal Original Research Article
lokal Gene Rearrangement [MeSH]
lokal Proto-Oncogene Proteins c-bcl-2/genetics [MeSH]
1000 Liste der Beteiligten
  1. https://orcid.org/0000-0001-5767-7125|https://frl.publisso.de/adhoc/uri/UmllZGwsIErDtnJn|https://frl.publisso.de/adhoc/uri/S8O8bnN0bmVyLCBBeGVs|https://frl.publisso.de/adhoc/uri/RsOkaG5yaWNoLCBBbmtl|https://frl.publisso.de/adhoc/uri/S2V0emVyLCBKdWxpdXM=|https://frl.publisso.de/adhoc/uri/RmxpZWRuZXIsIFN0ZXBoYW5pZSBNLiBKLg==|https://frl.publisso.de/adhoc/uri/UmVpbWVyLCBOaWtsYXM=|https://frl.publisso.de/adhoc/uri/QmVybmFyZCwgVmVyb25pY2E=|https://frl.publisso.de/adhoc/uri/dm9uIEJ1Ym5vZmYsIE5pa29sYXM=|https://frl.publisso.de/adhoc/uri/TWVyeiwgSGFydG11dA==|https://frl.publisso.de/adhoc/uri/QnVzY2gsIEhhdWtl|https://frl.publisso.de/adhoc/uri/RmVsbGVyLCBBbGZyZWQ=|https://frl.publisso.de/adhoc/uri/R2ViYXVlciwgTmlrbGFz
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