Mutational landscape of gray zone lymphoma
| Autor: | Anja Mottok, Gerben Duns, Lauren C. Chong, Camille Laurent, Katsuyoshi Takata, Susana Ben-Neriah, Adele Telenius, Alexandra Traverse-Glehen, David Scott, Graham W. Slack, Gilles Salles, Kerry J. Savage, Elizabeth A. Chavez, Aixiang Jiang, Tomoko Miyata-Takata, Peggy Dartigues, Stacy Hung, Clémentine Sarkozy, Christian Steidl, Diane Damotte, Tomohiro Aoki, Pedro Farinha, Thierry Jo Molina, René-Olivier Casasnovas |
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| Přispěvatelé: | Centre de Recherche en Cancérologie de Lyon (UNICANCER/CRCL), Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université de Paris - UFR Médecine Paris Centre [Santé] (UP Médecine Paris Centre), Université de Paris (UP), Centre de Recherche des Cordeliers (CRC (UMR_S_1138 / U1138)), École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université de Paris (UP), Centre de Recherches en Cancérologie de Toulouse (CRCT), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS) |
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
Male
Epstein-Barr Virus Infections protein p53 [SDV]Life Sciences [q-bio] medicine.disease_cause Biochemistry 0302 clinical medicine chlorambucil immune system diseases hemic and lymphatic diseases B-cell lymphoma genes Aged 80 and over 0303 health sciences Mutation chile Hematology Middle Aged BCL6 Hodgkin Disease 030220 oncology & carcinogenesis Female Lymphoma Large B-Cell Diffuse BLOOD Commentary Adult Adolescent Immunology lymphoma Thymus Gland Biology Mediastinal Neoplasms Gray zone lymphoma Young Adult 03 medical and health sciences medicine Humans human hodgkin's disease Aged 030304 developmental biology herpesvirus 4 Cell Biology medicine.disease GNA13 NFKBIE Lymphoma diffuse large b-cell lymphoma primary mediastinal large b-cell lymphoma Cancer research mutation Diffuse large B-cell lymphoma |
| Zdroj: | Blood Blood, American Society of Hematology, 2021, 137 (13), pp.1765-1776. ⟨10.1182/blood.2020007507⟩ |
| ISSN: | 0006-4971 1528-0020 |
| DOI: | 10.1182/blood.2020007507⟩ |
| Popis: | The mutational landscape of gray zone lymphoma (GZL) has not yet been established, and differences from related entities are largely unknown. Here, we studied coding sequence mutations of 50 Epstein-Barr virus (EBV)-negative GZLs and 20 polymorphic EBV+ diffuse large B-cell lymphoma (DLBCL) not otherwise specified (poly-EBV-L) in comparison with classical Hodgkin lymphoma (cHL), primary mediastinal large B-cell lymphoma (PMBCL), and DLBCL. Exomes of 21 GZL and 7 poly-EBV-L cases, along with paired constitutional DNA, were analyzed as a discovery cohort, followed by targeted sequencing of 217 genes in an extension cohort of 29 GZL and 13 poly-EBV-L cases. GZL cases with thymic niche involvement (anterior mediastinal mass) exhibited a mutation profile closely resembling cHL and PMBCL, with SOCS1 (45%), B2M (45%), TNFAIP3 (35%), GNA13 (35%), LRRN3 (32%), and NFKBIA (29%) being the most recurrently mutated genes. In contrast, GZL cases without thymic niche involvement (n = 18) had a significantly distinct pattern that was enriched in mutations related to apoptosis defects (TP53 [39%], BCL2 [28%], BIRC6 [22%]) and depleted in GNA13, XPO1, or NF-κB signaling pathway mutations (TNFAIP3, NFKBIE, IKBKB, NFKBIA). They also exhibited more BCL2/BCL6 rearrangements compared with thymic GZL. Poly-EBV-L cases presented a distinct mutational profile, including STAT3 mutations and a significantly lower coding mutation load in comparison with EBV− GZL. Our study highlights characteristic mutational patterns in GZL associated with presentation in the thymic niche, suggesting a common cell of origin and disease evolution overlapping with related anterior mediastinal lymphomas. |
| Databáze: | OpenAIRE |
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