Identification of primary mediastinal B-cell lymphomas with higher clonal dominance and poorer outcome using 5′RACE
Abstract: There is a scarcity of data on the tumor B-cell receptor (BCR) repertoire and lymphoid microenvironment in primary mediastinal B-cell lymphoma (PMBL). We applied 5ʹ rapid amplification of complimentary DNA ends (5′RACE) to tumor RNA samples from 137 patients with PMBL with available gene e...
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Elsevier
2025-01-01
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| Series: | Blood Advances |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2473952924005548 |
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| author | Vincent Camus Mathieu Viennot Pierre-Julien Viailly Fanny Drieux Elena-Liana Veresezan Victor Bobée Vinciane Rainville Elodie Bohers Pierre Sesques Corinne Haioun Eric Durot Michael Bayaram Cédric Rossi Laurent Martin Dominique Penther Sophie Kaltenbach Julie Bruneau Jérôme Paillassa Olivier Tournilhac Nicolas Gower Alexandre Willaume Chloé Antier Loïc Renaud Emilie Lévêque Pierre Decazes Stéphanie Becker David Tonnelet Philippe Gaulard Hervé Tilly Thierry Jo Molina Alexandra Traverse-Glehen Marie Donzel Philippe Ruminy Fabrice Jardin |
| author_facet | Vincent Camus Mathieu Viennot Pierre-Julien Viailly Fanny Drieux Elena-Liana Veresezan Victor Bobée Vinciane Rainville Elodie Bohers Pierre Sesques Corinne Haioun Eric Durot Michael Bayaram Cédric Rossi Laurent Martin Dominique Penther Sophie Kaltenbach Julie Bruneau Jérôme Paillassa Olivier Tournilhac Nicolas Gower Alexandre Willaume Chloé Antier Loïc Renaud Emilie Lévêque Pierre Decazes Stéphanie Becker David Tonnelet Philippe Gaulard Hervé Tilly Thierry Jo Molina Alexandra Traverse-Glehen Marie Donzel Philippe Ruminy Fabrice Jardin |
| author_sort | Vincent Camus |
| collection | DOAJ |
| description | Abstract: There is a scarcity of data on the tumor B-cell receptor (BCR) repertoire and lymphoid microenvironment in primary mediastinal B-cell lymphoma (PMBL). We applied 5ʹ rapid amplification of complimentary DNA ends (5′RACE) to tumor RNA samples from 137 patients with PMBL with available gene expression profiling and next-generation sequencing data. We obtained 5′RACE results for 75 of the 137 (54.7%) patients with the following clinical characteristics: median age (range), 33 years (18-64); female, 53.3%; performance status score 0 to 1, 86.7%; stage I to II, 57.3%; first-line treatment with anti-CD20 plus doxorubicin-based chemotherapy, 100%. Among the 60 biopsies that expressed a productive BCR, we highlighted a strong somatic hypermutation profile, defined as <98% identity to the germ line sequence, with 58 (96.7%) patients carrying mutated IgVH. We then identified a subgroup of 12 of the 75 patients (16%) with a worse prognosis (progression-free survival [PFS]: hazard ratio [HR], 17; overall survival [OS]: HR, 21) that was associated with the highest clonal dominance (HCD) status, defined as the dominant clonotype representing >81.1% and >78.6% of all complementarity-determining region 3 sequences for IgVH and IgVL, respectively. When compared with other patients, this subgroup had similar clinical characteristics but a greater median allele frequency for all somatic variants, a decreased BCR diversity, and greater expression of PDL1/PDL2 and MS4A1 genes, suggesting greater tumoral infiltration. We confirmed this poorer prognosis in a multivariate model and in an independent validation cohort in which 6 of 37 (16%) PMBL patients exhibited HCD (PFS: HR, 12; OS: HR, 17). |
| format | Article |
| id | doaj-art-20b3dcf06ab24e1b99600b2edfe81c81 |
| institution | DOAJ |
| issn | 2473-9529 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Elsevier |
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| series | Blood Advances |
| spelling | doaj-art-20b3dcf06ab24e1b99600b2edfe81c812025-08-20T02:39:48ZengElsevierBlood Advances2473-95292025-01-019110111510.1182/bloodadvances.2024013723Identification of primary mediastinal B-cell lymphomas with higher clonal dominance and poorer outcome using 5′RACEVincent Camus0Mathieu Viennot1Pierre-Julien Viailly2Fanny Drieux3Elena-Liana Veresezan4Victor Bobée5Vinciane Rainville6Elodie Bohers7Pierre Sesques8Corinne Haioun9Eric Durot10Michael Bayaram11Cédric Rossi12Laurent Martin13Dominique Penther14Sophie Kaltenbach15Julie Bruneau16Jérôme Paillassa17Olivier Tournilhac18Nicolas Gower19Alexandre Willaume20Chloé Antier21Loïc Renaud22Emilie Lévêque23Pierre Decazes24Stéphanie Becker25David Tonnelet26Philippe Gaulard27Hervé Tilly28Thierry Jo Molina29Alexandra Traverse-Glehen30Marie Donzel31Philippe Ruminy32Fabrice Jardin33Department of Hematology, Centre Henri Becquerel, Rouen, France; INSERM U1245, Centre Henri Becquerel, University of Rouen, Rouen, France; Correspondence: Vincent Camus, Department of Hematology, Centre Henri Becquerel, 1 Rue d’Amiens, 76038 Rouen Cedex, France;INSERM U1245, Centre Henri Becquerel, University of Rouen, Rouen, FranceINSERM U1245, Centre Henri Becquerel, University of Rouen, Rouen, FranceINSERM U1245, Centre Henri Becquerel, University of Rouen, Rouen, France; Department of Pathology, Centre Henri Becquerel, Rouen, FranceINSERM U1245, Centre Henri Becquerel, University of Rouen, Rouen, France; Department of Pathology, Centre Henri Becquerel, Rouen, FranceINSERM U1245, Centre Henri Becquerel, University of Rouen, Rouen, France; Biological Hematology Laboratory, Centre Hospitalier Universitaire de Rouen, Hôpital Charles Nicolle, Rouen, FranceINSERM U1245, Centre Henri Becquerel, University of Rouen, Rouen, FranceINSERM U1245, Centre Henri Becquerel, University of Rouen, Rouen, FranceDepartment of Hematology, Hospices Civils de Lyon, Pierre-Bénite, FranceDepartment of Lymphoid Malignancies, Centre Hospitalier Universitaire Henri Mondor, Assistance Publique-Hôpitaux de Paris, Créteil, FranceDepartment of Hematology, Centre Hospitalier Universitaire de Reims, Reims, FranceDepartment of Pathology, Centre Hospitalier Universitaire de Reims, Reims, FranceDepartment of Hematology, Centre Hospitalier Universitaire de Dijon, Dijon, FranceDepartment of Pathology, Centre Hospitalier Universitaire de Dijon, Dijon, FranceINSERM U1245, Centre Henri Becquerel, University of Rouen, Rouen, France; Laboratory of Genetic Oncology, Centre Henri Becquerel, Rouen, FranceCentre Hospitalier Universitaire Necker, Laboratory of Onco-Hematology, Assistance Publique-Hôpitaux de Paris, Paris, FranceUniversity of Paris, Institut Imagine, Institut des Maladies Génétiques, INSERM UMR1163, Paris, France; Department of Pathology, Université Paris Cité, Assistance Publique-Hôpitaux de Paris, Hôpitaux Necker et Robert Debré, Paris, FranceDepartment of Hematology, Centre Hospitalier Universitaire d’Angers, Angers, FranceDepartment of Hematology, Centre Hospitalier Universitaire de Clermont-Ferrand, Clermont-Ferrand, FranceDepartment of Hematology, Centre Hospitalier Universitaire de Lille, Hôpital Claude Hurriez, Lille, FranceDepartment of Hematology, Hôpital Saint Vincent de Paul, Groupe Hospitalier de l'Institut Catholique de Lille, Lille, FranceDepartment of Hematology, Centre Hospitalier Universitaire de Nantes, Nantes, FranceDepartment of Hematology, Gustave Roussy, Villejuif, FranceClinical Research Unit, Centre Henri Becquerel, Rouen, FranceDepartment of Nuclear Medicine and QuantIF-LITIS-EA4108, Centre Henri Becquerel, University of Rouen, Rouen, FranceDepartment of Pathology, Centre Hospitalier Universitaire Henri Mondor, Assistance Publique-Hôpitaux de Paris, Créteil, FranceDepartment of Nuclear Medicine and QuantIF-LITIS-EA4108, Centre Henri Becquerel, University of Rouen, Rouen, FranceDepartment of Pathology, Centre Hospitalier Universitaire Henri Mondor, Assistance Publique-Hôpitaux de Paris, Créteil, FranceDepartment of Hematology, Centre Henri Becquerel, Rouen, France; INSERM U1245, Centre Henri Becquerel, University of Rouen, Rouen, FranceUniversity of Paris, Institut Imagine, Institut des Maladies Génétiques, INSERM UMR1163, Paris, France; Department of Pathology, Université Paris Cité, Assistance Publique-Hôpitaux de Paris, Hôpitaux Necker et Robert Debré, Paris, FranceDepartment of Pathology, Hospices Civils de Lyon, Université Lyon 1, Pierre-Bénite, FranceDepartment of Pathology, Hospices Civils de Lyon, Université Lyon 1, Pierre-Bénite, FranceINSERM U1245, Centre Henri Becquerel, University of Rouen, Rouen, FranceDepartment of Hematology, Centre Henri Becquerel, Rouen, France; INSERM U1245, Centre Henri Becquerel, University of Rouen, Rouen, FranceAbstract: There is a scarcity of data on the tumor B-cell receptor (BCR) repertoire and lymphoid microenvironment in primary mediastinal B-cell lymphoma (PMBL). We applied 5ʹ rapid amplification of complimentary DNA ends (5′RACE) to tumor RNA samples from 137 patients with PMBL with available gene expression profiling and next-generation sequencing data. We obtained 5′RACE results for 75 of the 137 (54.7%) patients with the following clinical characteristics: median age (range), 33 years (18-64); female, 53.3%; performance status score 0 to 1, 86.7%; stage I to II, 57.3%; first-line treatment with anti-CD20 plus doxorubicin-based chemotherapy, 100%. Among the 60 biopsies that expressed a productive BCR, we highlighted a strong somatic hypermutation profile, defined as <98% identity to the germ line sequence, with 58 (96.7%) patients carrying mutated IgVH. We then identified a subgroup of 12 of the 75 patients (16%) with a worse prognosis (progression-free survival [PFS]: hazard ratio [HR], 17; overall survival [OS]: HR, 21) that was associated with the highest clonal dominance (HCD) status, defined as the dominant clonotype representing >81.1% and >78.6% of all complementarity-determining region 3 sequences for IgVH and IgVL, respectively. When compared with other patients, this subgroup had similar clinical characteristics but a greater median allele frequency for all somatic variants, a decreased BCR diversity, and greater expression of PDL1/PDL2 and MS4A1 genes, suggesting greater tumoral infiltration. We confirmed this poorer prognosis in a multivariate model and in an independent validation cohort in which 6 of 37 (16%) PMBL patients exhibited HCD (PFS: HR, 12; OS: HR, 17).http://www.sciencedirect.com/science/article/pii/S2473952924005548 |
| spellingShingle | Vincent Camus Mathieu Viennot Pierre-Julien Viailly Fanny Drieux Elena-Liana Veresezan Victor Bobée Vinciane Rainville Elodie Bohers Pierre Sesques Corinne Haioun Eric Durot Michael Bayaram Cédric Rossi Laurent Martin Dominique Penther Sophie Kaltenbach Julie Bruneau Jérôme Paillassa Olivier Tournilhac Nicolas Gower Alexandre Willaume Chloé Antier Loïc Renaud Emilie Lévêque Pierre Decazes Stéphanie Becker David Tonnelet Philippe Gaulard Hervé Tilly Thierry Jo Molina Alexandra Traverse-Glehen Marie Donzel Philippe Ruminy Fabrice Jardin Identification of primary mediastinal B-cell lymphomas with higher clonal dominance and poorer outcome using 5′RACE Blood Advances |
| title | Identification of primary mediastinal B-cell lymphomas with higher clonal dominance and poorer outcome using 5′RACE |
| title_full | Identification of primary mediastinal B-cell lymphomas with higher clonal dominance and poorer outcome using 5′RACE |
| title_fullStr | Identification of primary mediastinal B-cell lymphomas with higher clonal dominance and poorer outcome using 5′RACE |
| title_full_unstemmed | Identification of primary mediastinal B-cell lymphomas with higher clonal dominance and poorer outcome using 5′RACE |
| title_short | Identification of primary mediastinal B-cell lymphomas with higher clonal dominance and poorer outcome using 5′RACE |
| title_sort | identification of primary mediastinal b cell lymphomas with higher clonal dominance and poorer outcome using 5 race |
| url | http://www.sciencedirect.com/science/article/pii/S2473952924005548 |
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