Genomic and microenvironmental landscape of stage I follicular lymphoma, compared with stage III/IV
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- G. Tjitske Los-de Vries
- 1Department of Pathology, Amsterdam University Medical Center (UMC), Vrije Universiteit Amsterdam, Cancer Center Amsterdam, Amsterdam, The Netherlands;
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- Wendy B. C. Stevens
- 2Department of Hematology, Radboudumc Nijmegen, Nijmegen, The Netherlands;
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- Erik van Dijk
- 1Department of Pathology, Amsterdam University Medical Center (UMC), Vrije Universiteit Amsterdam, Cancer Center Amsterdam, Amsterdam, The Netherlands;
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- Carole Langois-Jacques
- 3Université Lyon 1, Villeurbanne, France, Centre National de la Recherche Scientifique (CNRS), Unité Mixte de recherche (UMR) 5558, Laboratoire de Biométrie et Biologie Évolutive, Équipe Biostatistique-Santé, Villeurbanne, France;
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- Andrew J. Clear
- 5Centre for Haemato-Oncology, Barts Cancer Institute, Queen Mary, University of London, London, United Kingdom;
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- Phylicia Stathi
- 1Department of Pathology, Amsterdam University Medical Center (UMC), Vrije Universiteit Amsterdam, Cancer Center Amsterdam, Amsterdam, The Netherlands;
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- Margaretha G. M. Roemer
- 1Department of Pathology, Amsterdam University Medical Center (UMC), Vrije Universiteit Amsterdam, Cancer Center Amsterdam, Amsterdam, The Netherlands;
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- Matias Mendeville
- 1Department of Pathology, Amsterdam University Medical Center (UMC), Vrije Universiteit Amsterdam, Cancer Center Amsterdam, Amsterdam, The Netherlands;
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- Nathalie J. Hijmering
- 1Department of Pathology, Amsterdam University Medical Center (UMC), Vrije Universiteit Amsterdam, Cancer Center Amsterdam, Amsterdam, The Netherlands;
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- Birgitta Sander
- 6Department of Laboratory Medicine, Division of Pathology, Karolinska Institute and Karolinska University Hospital, Stockholm, Sweden;
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- Andreas Rosenwald
- 7Institute of Pathology, University of Würzburg, Würzburg, and Comprehensive Cancer Center Mainfranken, Germany;
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- Maria Calaminici
- 5Centre for Haemato-Oncology, Barts Cancer Institute, Queen Mary, University of London, London, United Kingdom;
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- Eva Hoster
- 8Department of Medicine III, University Hospital Grosshadern, Munich, Germany;
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- Wolfgang Hiddemann
- 8Department of Medicine III, University Hospital Grosshadern, Munich, Germany;
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- Philippe Gaulard
- 10Department of Pathology, Henri Mondor University Hospital, Assistance Pyblique- Hospitaux de Paris (APHP), INSERM U955, Université Paris-Est, Créteil, France;
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- Gilles Salles
- 11Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY;
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- Heike Horn
- 12Institute for Clinical Pathology, Robert-Bosch-Krankenhaus, Dr. Margarete Fischer-Bosch-Institut für Klinische Pharmakologie, Stuttgart, Germany;
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- Wolfram Klapper
- 13Institute of Pathology, University of Schleswig-Holstein, Kiel, Germany;
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- Luc Xerri
- 14Département de Biopathologie, Institut Paoli-Calmettes, Marseille, France;
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- Catherine Burton
- 15Haematological Malignancy Diagnostic Service, St. James University Hospital, Leeds, United Kingdom;
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- Reuben M. Tooze
- 16Division of Haematology & Immunology, Leeds Institute of Medical Research, University of Leeds, Leeds, United Kingdom;
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- Alexandra G. Smith
- 17Epidemiology & Cancer Statistics Group, Department of Health Sciences, University of York, York, United Kingdom;
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- Christian Buske
- 18Institute of Experimental Cancer Research, Comprehensive Cancer Center (CCC) Ulm, Universitätsklinikum Ulm, Ulm, Germany;
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- David W. Scott
- 19BC Cancer Centre for Lymphoid Cancer and The University of British Columbia, Vancouver, BC, Canada;
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- Yasodha Natkunam
- 20Department of Pathology, and
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- Ranjana Advani
- 21Department of Hematology, Stanford University School of Medicine, Stanford Cancer Institute, Stanford, CA;
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- Laurie H. Sehn
- 19BC Cancer Centre for Lymphoid Cancer and The University of British Columbia, Vancouver, BC, Canada;
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- John Raemaekers
- 2Department of Hematology, Radboudumc Nijmegen, Nijmegen, The Netherlands;
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- John Gribben
- 5Centre for Haemato-Oncology, Barts Cancer Institute, Queen Mary, University of London, London, United Kingdom;
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- Eva Kimby
- 22Department of Medicine, Division of Hematology, Karolinska Institute, Stockholm, Sweden; and
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- Marie José Kersten
- 23Department of Hematology, Amsterdam University Medical Center (UMC), University of Amsterdam, Cancer Center Amsterdam, Amsterdam, The Netherlands
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- Delphine Maucort-Boulch
- 3Université Lyon 1, Villeurbanne, France, Centre National de la Recherche Scientifique (CNRS), Unité Mixte de recherche (UMR) 5558, Laboratoire de Biométrie et Biologie Évolutive, Équipe Biostatistique-Santé, Villeurbanne, France;
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- Bauke Ylstra
- 1Department of Pathology, Amsterdam University Medical Center (UMC), Vrije Universiteit Amsterdam, Cancer Center Amsterdam, Amsterdam, The Netherlands;
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- Daphne de Jong
- 1Department of Pathology, Amsterdam University Medical Center (UMC), Vrije Universiteit Amsterdam, Cancer Center Amsterdam, Amsterdam, The Netherlands;
抄録
<jats:title>Abstract</jats:title> <jats:p>Although the genomic and immune microenvironmental landscape of follicular lymphoma (FL) has been extensively investigated, little is known about the potential biological differences between stage I and stage III/IV disease. Using next-generation sequencing and immunohistochemistry, 82 FL nodal stage I cases were analyzed and compared with 139 FL stage III/IV nodal cases. Many similarities in mutations, chromosomal copy number aberrations, and microenvironmental cell populations were detected. However, there were also significant differences in microenvironmental and genomic features. CD8+ T cells (P = .02) and STAT6 mutations (false discovery rate [FDR] <0.001) were more frequent in stage I FL. In contrast, programmed cell death protein 1–positive T cells, CD68+/CD163+ macrophages (P < .001), BCL2 translocation (BCL2trl+) (P < .0001), and KMT2D (FDR = 0.003) and CREBBP (FDR = 0.04) mutations were found more frequently in stage III/IV FL. Using clustering, we identified 3 clusters within stage I, and 2 clusters within stage III/IV. The BLC2trl+ stage I cluster was comparable to the BCL2trl+ cluster in stage III/IV. The two BCL2trl– stage I clusters were unique for stage I. One was enriched for CREBBP (95%) and STAT6 (64%) mutations, without BLC6 translocation (BCL6trl), whereas the BCL2trl– stage III/IV cluster contained BCL6trl (64%) with fewer CREBBP (45%) and STAT6 (9%) mutations. The other BCL2trl– stage I cluster was relatively heterogeneous with more copy number aberrations and linker histone mutations. This exploratory study shows that stage I FL is genetically heterogeneous with different underlying oncogenic pathways. Stage I FL BCL2trl– is likely STAT6 driven, whereas BCL2trl– stage III/IV appears to be more BCL6trl driven.</jats:p>
収録刊行物
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- Blood Advances
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Blood Advances 6 (18), 5482-5493, 2022-09-26
American Society of Hematology