Evidence map›Paper›PMID 29713087›Full record

ArticleNature medicine2018

Molecular subtypes of diffuse large B cell lymphoma are associated with distinct pathogenic mechanisms and outcomes.

Bjoern Chapuy, Chip Stewart, Andrew J Dunford, Jaegil Kim, Atanas Kamburov, Robert A Redd, Mike S Lawrence, Margaretha G M Roemer, Amy J Li, Marita Ziepert and 36 more

Erratum issued Registry-linked trialOpen access · greenAbstract readMulticenter Study
PubMed Full text at PMC Publisher
In one paragraph

Article in Nature medicine, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. It is linked to trial NCT06339255 (A Multicenter Prospective Observational Study on Chimeric Antigen Receptor), which is not on this map. Cited by 1,189 papers.

0numbers the graph read from it
0cells of the map it votes in
1,189citing papers in PubMed
121.7field-weighted citation impact, top 1% 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.

NCT06339255 recruitingnot on this mapstarted 2019, after this paper: background citation

A Multicenter Prospective Observational Study on Chimeric Antigen Receptor (CAR) T-cell Therapy for Lymphoma: Monitoring Feasibility, Efficacy, Toxicity and Biomarkers in a Real Life Setting

TypeobservationalSponsorPaolo CorradiniRan2019 to 2029Enrolled5,300ConditionsDiffuse Low Grade B-Cell Lymphoma, Primary Mediastinal Large B-cell Lymphoma (PMBCL), Mantle Cell Lymphoma, Follicular Lymphoma
3 · Its place in the literature

Who cites it

1,189 citing papers in PubMed, 1,920 citations in OpenAlex.

  1. Trial
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  3. Impact of a Virtual Multidisciplinary Lymphoma Tumor Board on Clinical Decision-Making.Mayo Clinic proceedings. Innovations, quality & outcomes · 2026
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  20. Heterogeneity in primary gastrointestinal DLBCL: from clinical management to molecular mechanisms and treatment strategies.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2026
    Review

1,129 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

46 authors at 14 institutions in 2 countries.

Bjoern Chapuy *Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
Chip Stewart *Broad Institute of Harvard and Massachusetts Institute of Technology, Cambridge, MA, USA.
Andrew J Dunford *Broad Institute of Harvard and Massachusetts Institute of Technology, Cambridge, MA, USA.
Jaegil KimBroad Institute of Harvard and Massachusetts Institute of Technology, Cambridge, MA, USA.
Atanas KamburovBroad Institute of Harvard and Massachusetts Institute of Technology, Cambridge, MA, USA.
Robert A ReddBiostatistics and Computational Biology, Dana-Farber Cancer Institute, Boston, MA, USA.
Mike S LawrenceHarvard Medical School, Boston, MA, USA.
Margaretha G M RoemerDepartment of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
Amy J LiBoston University School of Medicine, Section of Computational Biomedicine, Boston, MA, USA.
Marita ZiepertInstitute for Medical Informatics, Statistics and Epidemiology, University Leipzig, Leipzig, Germany.
Annette M StaigerDr. Margarete Fischer-Bosch Institute of Clinical Pharmacology, Stuttgart, and University of Tuebingen, Tuebingen, Germany.ORCID http://orcid.org/0000-0002-5896-3200
Jeremiah A WalaBroad Institute of Harvard and Massachusetts Institute of Technology, Cambridge, MA, USA.ORCID http://orcid.org/0000-0001-6591-1620
Matthew D DucarDana-Farber Cancer Institute, Center for Cancer Genome Discovery, Boston, MA, USA.
Ignaty LeshchinerBroad Institute of Harvard and Massachusetts Institute of Technology, Cambridge, MA, USA.ORCID http://orcid.org/0000-0001-8942-9265
Ester RheinbayBroad Institute of Harvard and Massachusetts Institute of Technology, Cambridge, MA, USA.
Amaro Taylor-WeinerBroad Institute of Harvard and Massachusetts Institute of Technology, Cambridge, MA, USA.
Caroline A CoughlinDepartment of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
Julian M HessBroad Institute of Harvard and Massachusetts Institute of Technology, Cambridge, MA, USA.
Chandra S PedamalluBroad Institute of Harvard and Massachusetts Institute of Technology, Cambridge, MA, USA.
Dimitri LivitzBroad Institute of Harvard and Massachusetts Institute of Technology, Cambridge, MA, USA.ORCID http://orcid.org/0000-0003-2528-1446
Daniel RosebrockBroad Institute of Harvard and Massachusetts Institute of Technology, Cambridge, MA, USA.
Mara RosenbergBroad Institute of Harvard and Massachusetts Institute of Technology, Cambridge, MA, USA.
Adam A TracyBroad Institute of Harvard and Massachusetts Institute of Technology, Cambridge, MA, USA.
Heike HornDr. Margarete Fischer-Bosch Institute of Clinical Pharmacology, Stuttgart, and University of Tuebingen, Tuebingen, Germany.
Paul van HummelenDana-Farber Cancer Institute, Center for Cancer Genome Discovery, Boston, MA, USA.
Andrew L FeldmanMayo Clinic, Rochester, MN, USA.ORCID http://orcid.org/0000-0001-5009-4808
Brian K LinkUniversity of Iowa, Iowa City, IA, USA.
Anne J NovakMayo Clinic, Rochester, MN, USA.
James R CerhanMayo Clinic, Rochester, MN, USA.
Thomas M HabermannMayo Clinic, Rochester, MN, USA.
Reiner SiebertDepartment for Human Genetics, University Ulm, Ulm, Germany.
Andreas RosenwaldDepartment of Pathology, University of Würzburg, Würzburg, Germany.
Aaron R ThornerDana-Farber Cancer Institute, Center for Cancer Genome Discovery, Boston, MA, USA.
Matthew L MeyersonHarvard Medical School, Boston, MA, USA.ORCID http://orcid.org/0000-0002-9133-8108
Todd R GolubHarvard Medical School, Boston, MA, USA.ORCID http://orcid.org/0000-0003-0113-2403
Rameen BeroukhimHarvard Medical School, Boston, MA, USA.
Gerald G WulfDepartment of Hematology and Oncology, Georg-August University Göttingen, Göttingen, Germany.
German OttDepartment of Clinical Pathology, Robert-Bosch Krankenhaus, Stuttgart, Germany.
Scott J RodigHarvard Medical School, Boston, MA, USA.
Stefano MontiBoston University School of Medicine, Section of Computational Biomedicine, Boston, MA, USA.
Donna S NeubergHarvard Medical School, Boston, MA, USA.ORCID http://orcid.org/0000-0003-2566-3145
Markus LoefflerInstitute for Medical Informatics, Statistics and Epidemiology, University Leipzig, Leipzig, Germany.
Michael PfreundschuhDepartment of Medicine I, Saarland University, Homburg, Germany.
Lorenz TrümperDepartment of Hematology and Oncology, Georg-August University Göttingen, Göttingen, Germany.
Gad GetzHarvard Medical School, Boston, MA, USA. gadgetz@broadinstitute.org.ORCID http://orcid.org/0000-0002-0936-0753
Margaret A ShippDepartment of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA. margaret_shipp@dfci.harvard.edu.
Broad Institute · USDana-Farber Cancer Institute · USMayo Clinic in Arizona · USHarvard University · USBoston University · USLeipzig University · DERobert Bosch Hospital · DEUniversity of Göttingen · DEBrigham and Women's Hospital · USDr. Margarete Fischer-Bosch-Institute of Clinical Pharmacology · DESaarland University · DEUniversität Ulm · DEUniversity of Iowa · USUniversity of Würzburg · DE

Funding

Large Scale Sequencing and Analysis of GenomesU54HG003067 · NHGRI · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · PI GABRIEL, STACEY, LANDER, ERIC S · 2004 to 2015
$568.6M
Viral VectorP30CA086862 · NCI · UNIVERSITY OF IOWA · PI Douglas Robert Spitz · 2000 to 2026
$70.0M
The Role of Monocytes in non-Hodgkin LymphomaP50CA097274 · NCI · UNIVERSITY OF IOWA · PI WEINER, GEORGE J. · 2002 to 2021
$45.7M
Transcriptional mechanisms and melanomaP01CA163222 · NCI · MASSACHUSETTS GENERAL HOSPITAL · PI Kai W Wucherpfennig · 2013 to 2026
$25.3M
The Cancer Genome Atlas Data Analysis CenterU24CA143845 · NCI · BROAD INSTITUTE, INC. · PI CHIN, LYNDA, GETZ, GAD A · 2009 to 2016
$16.0M
Training Program in Bioinformatics and Integrative GenomicsT32HG002295 · NHGRI · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · PI Peter J Park · 2001 to 2026
$15.8M
Personal tumor neoantigens for immunity against chronic lymphocytic leukemiaR01CA155010 · NCI · DANA-FARBER CANCER INST · PI Catherine Ju-Ying Wu · 2011 to 2026
$9.6M
Global Infrastructure for Collaborative High-throughput Cancer Genomics AnalysisU24CA210999 · NCI · BROAD INSTITUTE, INC. · PI GETZ, GAD A · 2016 to 2020
$4.7M
NCI NIH HHS P01 CA163222NCI NIH HHS P50 CA097274NCI NIH HHS R01 CA155010NCI NIH HHS U24 CA143845NCI NIH HHS U24 CA210999NHGRI NIH HHS T32 HG002295NHGRI NIH HHS U54 HG003067
6 · The paper itself

Abstract

Diffuse large B cell lymphoma (DLBCL), the most common lymphoid malignancy in adults, is a clinically and genetically heterogeneous disease that is further classified into transcriptionally defined activated B cell (ABC) and germinal center B cell (GCB) subtypes. We carried out a comprehensive genetic analysis of 304 primary DLBCLs and identified low-frequency alterations, captured recurrent mutations, somatic copy number alterations, and structural variants, and defined coordinate signatures in patients with available outcome data. We integrated these genetic drivers using consensus clustering and identified five robust DLBCL subsets, including a previously unrecognized group of low-risk ABC-DLBCLs of extrafollicular/marginal zone origin; two distinct subsets of GCB-DLBCLs with different outcomes and targetable alterations; and an ABC/GCB-independent group with biallelic inactivation of TP53, CDKN2A loss, and associated genomic instability. The genetic features of the newly characterized subsets, their mutational signatures, and the temporal ordering of identified alterations provide new insights into DLBCL pathogenesis. The coordinate genetic signatures also predict outcome independent of the clinical International Prognostic Index and suggest new combination treatment strategies. More broadly, our results provide a roadmap for an actionable DLBCL classification.

Indexed as

DNA Copy Number VariationsGene RearrangementGenes, NeoplasmGenetic HeterogeneityHumansLymphoma, Large B-Cell, DiffuseMutationMutation RateTreatment Outcome

Identifiers

PMID29713087
PMCPMC6613387
OpenAlexW2801763724

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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.