Evidence map›Paper›PMID 25189415›Full record

ArticleLeukemia2015

The mutational pattern of primary lymphoma of the central nervous system determined by whole-exome sequencing.

I Vater, M Montesinos-Rongen, M Schlesner, A Haake, F Purschke, R Sprute, N Mettenmeyer, I Nazzal, I Nagel, J Gutwein and 7 more

Registry-linked trialAbstract read
PubMed Publisher
In one paragraph

Article in Leukemia, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT04066920 (Clinical Efficacy and Safety of IBER Salvage Treatment Followed by Ibrutinib Maintenance for Transplant-ineligible Patients With Relapsed or Refractory Primary Central Nervous System Lymphoma), which is not on this map. Cited by 82 papers.

0numbers the graph read from it
0cells of the map it votes in
82citing papers in PubMed
7.5field-weighted citation impact, top 2% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

NCT04066920 phase2unknown statusnot on this mapstarted 2019, after this paper: background citation

Clinical Efficacy and Safety of IBER Salvage Treatment Followed by Ibrutinib Maintenance for Transplant-ineligible Patients With Relapsed or Refractory Primary Central Nervous System Lymphoma (PCNSL): a Multicenter, Single-arm, Prospective Phase II Study

TypeinterventionalSponsorDeok-Hwan YangRan2019 to 2023Enrolled30ConditionsPrimary Central Nervous System LymphomaArmsIBER salvage chemotherapy followed by ibrutinib maintenance therapy
3 · Its place in the literature

Who cites it

82 citing papers in PubMed, 160 citations in OpenAlex.

  1. A Phase II Study Assessing Long-term Response to Ibrutinib Monotherapy in Recurrent or Refractory CNS Lymphoma.Clinical cancer research : an official journal of the American Association for Cancer Research · 2024
    Trial
  2. Review
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  15. Primary central nervous system lymphoma.Nature reviews. Disease primers · 2023
    Review
  16. Review
  17. Review
  18. Article
  19. Article
  20. Lymphomas of Central Nervous System.Advances in experimental medicine and biology · 2023
    Article

22 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

17 authors at 6 institutions in 1 country.

I VaterInstitute of Human Genetics, Christian-Albrechts-University Kiel & University Hospital Schleswig-Holstein, Campus Kiel, Kiel, Germany.
M Montesinos-RongenInstitute of Neuropathology, University of Cologne, Cologne, Germany.
M SchlesnerDivision of Theoretical Bioinformatics (B080), German Cancer Research Center (DKFZ), Heidelberg, Germany.
A HaakeInstitute of Human Genetics, Christian-Albrechts-University Kiel & University Hospital Schleswig-Holstein, Campus Kiel, Kiel, Germany.
F PurschkeInstitute of Neuropathology, University of Cologne, Cologne, Germany.
R SpruteInstitute of Neuropathology, University of Cologne, Cologne, Germany.
N MettenmeyerInstitute of Neuropathology, University of Cologne, Cologne, Germany.
I NazzalInstitute of Neuropathology, University of Cologne, Cologne, Germany.
I NagelInstitute of Human Genetics, Christian-Albrechts-University Kiel & University Hospital Schleswig-Holstein, Campus Kiel, Kiel, Germany.
J GutweinInstitute of Human Genetics, Christian-Albrechts-University Kiel & University Hospital Schleswig-Holstein, Campus Kiel, Kiel, Germany.
J RichterInstitute of Human Genetics, Christian-Albrechts-University Kiel & University Hospital Schleswig-Holstein, Campus Kiel, Kiel, Germany.
I BuchhalterDivision of Theoretical Bioinformatics (B080), German Cancer Research Center (DKFZ), Heidelberg, Germany.
R B Russell1] Cell Networks, University of Heidelberg, Heidelberg, Germany [2] BioQuant, Heidelberg University, Heidelberg, Germany.
O D WiestlerGerman Cancer Research Center (DKFZ), Heidelberg, Germany.
R Eils1] Division of Theoretical Bioinformatics (B080), German Cancer Research Center (DKFZ), Heidelberg, Germany [2] BioQuant, Heidelberg University, Heidelberg, Germany [3] Department for Bioinformatics and Functional Genomics, Institute for Pharmacy and Molecular Biotechnology (IPMB), Heidelberg University, Heidelberg, Germany.
M DeckertInstitute of Neuropathology, University of Cologne, Cologne, Germany.
R SiebertInstitute of Human Genetics, Christian-Albrechts-University Kiel & University Hospital Schleswig-Holstein, Campus Kiel, Kiel, Germany.
University of Cologne · DEHeidelberg University · DEUniversity of Lübeck · DEGerman Cancer Research Center · DEKiel University · DEUniversity Hospital Schleswig-Holstein · DE

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

To decipher the mutational pattern of primary CNS lymphoma (PCNSL), we performed whole-exome sequencing to a median coverage of 103 × followed by mutation verification in 9 PCNSL and validation using Sanger sequencing in 22 PCNSL. We identified a median of 202 (range: 139-251) potentially somatic single nucleotide variants (SNV) and 14 small indels (range: 7-22) with potentially protein-changing features per PCNSL. Mutations affected the B-cell receptor, toll-like receptor, and NF-κB and genes involved in chromatin structure and modifications, cell-cycle regulation, and immune recognition. A median of 22.2% (range: 20.0-24.7%) of somatic SNVs in 9 PCNSL overlaps with the RGYW motif targeted by somatic hypermutation (SHM); a median of 7.9% (range: 6.2-12.6%) affects its hotspot position suggesting a major impact of SHM on PCNSL pathogenesis. In addition to the well-known targets of aberrant SHM (aSHM) (PIM1), our data suggest new targets of aSHM (KLHL14, OSBPL10, and SUSD2). Among the four most frequently mutated genes was ODZ4 showing protein-changing mutations in 4/9 PCNSL. Together with mutations affecting CSMD2, CSMD3, and PTPRD, these findings may suggest that alterations in genes having a role in CNS development may facilitate diffuse large B-cell lymphoma manifestation in the CNS. This may point to intriguing mechanisms of CNS tropism in PCNSL.

Indexed as

ExomePolymorphism, GeneticSomatic Hypermutation, ImmunoglobulinAdultAgedCentral Nervous System NeoplasmsFemaleGenetic LociHigh-Throughput Nucleotide SequencingHumansImmunoglobulin Heavy ChainsLymphoma, Large B-Cell, DiffuseMaleMembrane GlycoproteinsMembrane ProteinsMiddle AgedCSMD2 protein, humanCSMD3 protein, humanImmunoglobulin Heavy ChainsMembrane GlycoproteinsMembrane ProteinsOxysterol Binding ProteinsPIM1 protein, humanProto-Oncogene Proteins c-pim-1PTPRD protein, humanReceptor-Like Protein Tyrosine Phosphatases, Class 2Receptors, SteroidSUSD2 protein, humanTENM4 protein, human

Identifiers

PMID25189415
OpenAlexW2040485091

What OpenQuestion holds

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Registered trials

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.