| Affiliation: | 1. Laboratory of Experimental Oncology and Lymphoma Unit, Oncology Institute of Southern Switzerland (IOSI), Bellinzona, Switzerland;2. Equally contributed.;3. Division of Haematology, Azienda Ospedaliera S. Maurizio, Bolzano/Bozen, Italy;4. Department of Pathology and Microbiology, University of Nebraska, Omaha, NE, USA;5. Istituto Dalle Molle di Studi sull’Intelligenza Artificiale, Manno, Switzerland;6. Department of Pathology and Centre for Experimental Research and Medical Studies (CeRMS), University of Turin, Turin, Italy;7. Department of Oncology and Haematology, Haematology 2 section, AOU San Giovanni Battista, Torino;8. UO Ematologia 1/CTMO, Università degli Studi di Milano, Dipartimento di Scienze Mediche, Ospedale Maggiore Policlinico MaRe, IRCCS, Milano;9. San Raffaele H Scientific Institute, Pathology Unit and Unit of Lymphoid Malignancies, Milan;10. Division of Haematology, Department of Clinical and Experimental Medicine & BRMA, Amedeo Avogadro University of Eastern Piedmont, Novara, Italy;11. Programa de Patologia Molecular, Centro Nacional de Investigaciones Oncologicas, Madrid, Spain;12. Department of Pathology, University of Brescia, I Servizio di Anatomia Patologica, and Division of Haematology, Spedali Civili di Brescia, Brescia, Italy;13. Department of Haematology and Laboratori d’Hematologia, Hospital de la Santa Creu i Sant Pau, Universitat Autònoma de Barcelona, Barcelona, Spain;14. Departments of Internal Medicine and of Pathology, University Hospital of Bicêtre, AP/HP, Le Kremlin Bicêtre, France;15. Anatomic Pathology Unit and Department of Oncology, University of Insubria, Ospedale di Circolo, Varese;16. Division of Pathology and Laboratory Medicine and Division of Haematology, European Institute of Oncology, Milan, Italy;17. Department of Pathology & Laboratory Medicine, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA |
| Abstract: | Despite recent therapeutic improvements, the clinical course of diffuse large B‐cell lymphoma (DLBCL) still differs considerably among patients. We conducted this retrospective multi‐centre study to evaluate the impact of genomic aberrations detected using a high‐density genome wide‐single nucleotide polymorphism‐based array on clinical outcome in a population of DLBCL patients treated with R‐CHOP‐21 (rituximab, cyclophosphamide, doxorubicine, vincristine and prednisone repeated every 21 d). 166 DNA samples were analysed using the GeneChip Human Mapping 250K NspI. Genomic anomalies were analysed regarding their impact on the clinical course of 124 patients treated with R‐CHOP‐21. Unsupervised clustering was performed to identify genetically related subgroups of patients with different clinical outcomes. Twenty recurrent genetic lesions showed an impact on the clinical course. Loss of genomic material at 8p23.1 showed the strongest statistical significance and was associated with additional aberrations, such as 17p‐ and 15q‐. Unsupervised clustering identified five DLBCL clusters with distinct genetic profiles, clinical characteristics and outcomes. Genetic features and clusters, associated with a different outcome in patients treated with R‐CHOP, have been identified by arrayCGH. |
