Evidence map›Paper›PMID 31697821›Full record

ArticleBlood2019

Genomic analyses of PMBL reveal new drivers and mechanisms of sensitivity to PD-1 blockade.

Bjoern Chapuy, Chip Stewart, Andrew J Dunford, Jaegil Kim, Kirsty Wienand, Atanas Kamburov, Gabriel K Griffin, Pei-Hsuan Chen, Ana Lako, Robert A Redd and 6 more

Open access · bronzeAbstract read
In one paragraph

Article in Blood, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 62 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
62citing papers in PubMed, 1 pooled it
5.3field-weighted citation impact, top 3% 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.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

62 citing papers in PubMed, 1 synthesis or guideline pooled it, 104 citations in OpenAlex.

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  11. Xq24/HemaSphere · 2025
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2 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

16 authors at 4 institutions in 2 countries.

Bjoern ChapuyDepartment of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA.
Chip StewartBroad Institute of Harvard and Massachusetts Institute of Technology, Cambridge, MA.
Andrew J DunfordBroad Institute of Harvard and Massachusetts Institute of Technology, Cambridge, MA.
Jaegil KimBroad Institute of Harvard and Massachusetts Institute of Technology, Cambridge, MA.
Kirsty WienandDepartment of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA.
Atanas KamburovBroad Institute of Harvard and Massachusetts Institute of Technology, Cambridge, MA.
Gabriel K GriffinDepartment of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA.
Pei-Hsuan ChenDepartment of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA.
Ana LakoDepartment of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA.
Robert A ReddDepartment of Data Sciences and.
Claire M CoteDepartment of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA.
Matthew D DucarCenter for Cancer Genome Discovery, Dana-Farber Cancer Institute, Boston, MA; and.
Aaron R ThornerCenter for Cancer Genome Discovery, Dana-Farber Cancer Institute, Boston, MA; and.
Scott J RodigDepartment of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA.
Gad GetzBroad Institute of Harvard and Massachusetts Institute of Technology, Cambridge, MA.
Margaret A ShippDepartment of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA.
Broad Institute · USBrigham and Women's Hospital · USHarvard University · USDana-Farber Cancer Institute · US

Funding

Targetable Immune Evasion Pathways in Hodgkin LymphomaR01CA161026 · NCI · DANA-FARBER CANCER INST · PI SHIPP, MARGARET A · 2011 to 2020
$4.0M
NCI NIH HHS R01 CA161026
6 · The paper itself

Abstract

Primary mediastinal large B-cell lymphomas (PMBLs) are aggressive tumors that typically present as large mediastinal masses in young women. PMBLs share clinical, transcriptional, and molecular features with classical Hodgkin lymphoma (cHL), including constitutive activation of nuclear factor κB (NF-κB), JAK/STAT signaling, and programmed cell death protein 1 (PD-1)-mediated immune evasion. The demonstrated efficacy of PD-1 blockade in relapsed/refractory PMBLs led to recent approval by the US Food and Drug Administration and underscored the importance of characterizing targetable genetic vulnerabilities in this disease. Here, we report a comprehensive analysis of recurrent genetic alterations -somatic mutations, somatic copy number alterations, and structural variants-in a cohort of 37 newly diagnosed PMBLs. We identified a median of 9 genetic drivers per PMBL, including known and newly identified components of the JAK/STAT and NF-κB signaling pathways and frequent B2M alterations that limit major histocompatibility complex class I expression, as in cHL. PMBL also exhibited frequent, newly identified driver mutations in ZNF217 and an additional epigenetic modifier, EZH2. The majority of these alterations were clonal, which supports their role as early drivers. In PMBL, we identified several previously uncharacterized molecular features that may increase sensitivity to PD-1 blockade, including high tumor mutational burden, microsatellite instability, and an apolipoprotein B mRNA editing catalytic polypeptide-like (APOBEC) mutational signature. The shared genetic features between PMBL and cHL provide a framework for analyzing the mechanism of action of PD-1 blockade in these related lymphoid malignancies.

Indexed as

Gene Expression Regulation, NeoplasticMutationAdultAntineoplastic Agents, ImmunologicalBiomarkers, TumorCohort StudiesDNA Copy Number VariationsFemaleGenomicsHumansLymphoma, Large B-Cell, DiffuseMaleMediastinal NeoplasmsPrognosisProgrammed Cell Death 1 ReceptorTrans-ActivatorsAntineoplastic Agents, ImmunologicalBiomarkers, TumorPDCD1 protein, humanProgrammed Cell Death 1 ReceptorTrans-ActivatorsZNF217 protein, human

Identifiers

PMID31697821
PMCPMC6933293
OpenAlexW2982701987

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

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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.