Evidence map›Paper›PMID 39992429›Full record

ArticleAnnals of hematology2025

The mutational landscape and its longitudinal dynamics in relapsed and refractory classic Hodgkin lymphoma.

Hanno Witte, Axel Künstner, Thomas Hahn, Veronica Bernard, Stephanie Stölting, Kathrin Kusch, Kumar Nagarathinam, Cyrus Khandanpour, Nikolas von Bubnoff, Arthur Bauer and 8 more

Abstract read
In one paragraph

Article in Annals of hematology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
–field-weighted citation impact
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

0 citing papers in PubMed.

No citing paper in PubMed yet.

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

18 authors.

Hanno Witte *University Cancer Center Schleswig-Holstein, University Hospital of Schleswig-Holstein, Campus Lübeck, 23538, Lübeck, Germany. hanno.witte@uni-ulm.de.
Axel Künstner *University Cancer Center Schleswig-Holstein, University Hospital of Schleswig-Holstein, Campus Lübeck, 23538, Lübeck, Germany.
Thomas Hahn *University Cancer Center Schleswig-Holstein, University Hospital of Schleswig-Holstein, Campus Lübeck, 23538, Lübeck, Germany.
Veronica BernardHämatopathologie Lübeck, Reference Centre for Lymph Node Pathology and Hematopathology, Maria-Goeppert-Straße 9a, 23562, Lübeck, Germany.
Stephanie StöltingHämatopathologie Lübeck, Reference Centre for Lymph Node Pathology and Hematopathology, Maria-Goeppert-Straße 9a, 23562, Lübeck, Germany.
Kathrin KuschHämatopathologie Lübeck, Reference Centre for Lymph Node Pathology and Hematopathology, Maria-Goeppert-Straße 9a, 23562, Lübeck, Germany.
Kumar NagarathinamInstitute of Biochemistry, University of Lübeck, Ratzeburger Allee 160, 23538, Lübeck, Germany.
Cyrus KhandanpourUniversity Cancer Center Schleswig-Holstein, University Hospital of Schleswig-Holstein, Campus Lübeck, 23538, Lübeck, Germany.
Nikolas von BubnoffUniversity Cancer Center Schleswig-Holstein, University Hospital of Schleswig-Holstein, Campus Lübeck, 23538, Lübeck, Germany.
Arthur BauerDepartment of Hematology and Oncology, Bundeswehrkrankenhaus Ulm, Oberer Eselsberg 40, 89081, Ulm, Germany.
Michael GrunertDepartment of Nuclear Medicine, Bundeswehrkrankenhaus Ulm, Oberer Eselsberg 40, 89081, Ulm, Germany.
Svenja HartungInstitute of Pathology, University Ulm, Albert-Einstein Allee 23, 89081, Ulm, Germany.
Annette ArndtInstitute of Pathology and Molecularpathology, Bundeswehrkrankenhaus Ulm, Oberer Eselsberg 40, 89081, Ulm, Germany.
Konrad SteinestelInstitute of Pathology and Molecularpathology, Bundeswehrkrankenhaus Ulm, Oberer Eselsberg 40, 89081, Ulm, Germany.
Hartmut MerzHämatopathologie Lübeck, Reference Centre for Lymph Node Pathology and Hematopathology, Maria-Goeppert-Straße 9a, 23562, Lübeck, Germany.
Hauke BuschUniversity Cancer Center Schleswig-Holstein, University Hospital of Schleswig-Holstein, Campus Lübeck, 23538, Lübeck, Germany.
Alfred C FellerHämatopathologie Lübeck, Reference Centre for Lymph Node Pathology and Hematopathology, Maria-Goeppert-Straße 9a, 23562, Lübeck, Germany.
Niklas GebauerUniversity Cancer Center Schleswig-Holstein, University Hospital of Schleswig-Holstein, Campus Lübeck, 23538, Lübeck, Germany.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

In classic Hodgkin-lymphoma (cHL), only a few cases recur, and only a limited fraction of patients is primary-refractory to standard-polychemotherapy. Underlying genomic features of unfavorable clinical courses remain sparsely characterized. Here, we investigated the genomic characteristics of primary-refractory/relapsed cHL in contrast with responders. Therefore, ultra-deep next-generation panel-sequencing was performed on a total of 59 FFPE-samples (20 responders, 26 relapsed (rHL: 11 initial-diagnosis, 15 relapse) and 13 primary-refractory (prHL: 8 initial-diagnosis, 5 progression) from 44 cHL-patients applying a hybrid-capture approach. We compared samples associated with distinct disease courses concerning their oncogenic drivers, mutational signatures, and perturbed pathways. Compared to responders, mutations in genes such as PMS2, PDGFRB, KAT6A, EPHB1, and HGF were detected more frequently in prHL/rHL. Additionally, we observed that in rHL or prHL, BARD1-mutations occur, whereas ETV1, NF1, and MET-mutations were eliminated through clonal selection. A significant enrichment of non-synonymous variants was detected in prHL compared to responders and a significant selection process in favor of NOTCH-pathway mutations driving rHL or prHL was observed. However, our analysis revealed a negative selection process for non-synonymous variants affecting the hippo-pathway. This study delineates distinct mutational signatures between responders and rHL/prHL, whilst illustrating longitudinal dynamics in mutational profiles using paired samples. Further, several exploitable therapeutic vulnerabilities for rHL and prHL were identified.

Indexed as

Hodgkin DiseaseMutationNeoplasm ProteinsAdolescentAdultAgedFemaleHigh-Throughput Nucleotide SequencingHumansLongitudinal StudiesMaleMiddle AgedNeoplasm Recurrence, LocalRecurrenceYoung AdultNeoplasm ProteinsClonal evolutionMutational landscapeRelapsed/refractory classic Hodgkin lymphomaUltra-deep sequencing

Identifiers

PMID39992429
PMCPMC12031843

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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.