Journal article
Molecular subtypes of diffuse large B cell lymphoma are associated with distinct pathogenic mechanisms and outcomes
Nature medicine, Vol.24(5), pp.679-690
05/2018
DOI: 10.1038/s41591-018-0016-8
PMCID: PMC6613387
PMID: 29713087
Abstract
Diffuse large B cell lymphoma (DLBCL), the most common lymphoid malignancy in adults, is a clinically and genetically heterogeneous disease that is further classified into transcriptionally defined activated B cell (ABC) and germinal center B cell (GCB) subtypes. We carried out a comprehensive genetic analysis of 304 primary DLBCLs and identified low-frequency alterations, captured recurrent mutations, somatic copy number alterations, and structural variants, and defined coordinate signatures in patients with available outcome data. We integrated these genetic drivers using consensus clustering and identified five robust DLBCL subsets, including a previously unrecognized group of low-risk ABC-DLBCLs of extrafollicular/marginal zone origin; two distinct subsets of GCB-DLBCLs with different outcomes and targetable alterations; and an ABC/GCB-independent group with biallelic inactivation of TP53, CDKN2A loss, and associated genomic instability. The genetic features of the newly characterized subsets, their mutational signatures, and the temporal ordering of identified alterations provide new insights into DLBCL pathogenesis. The coordinate genetic signatures also predict outcome independent of the clinical International Prognostic Index and suggest new combination treatment strategies. More broadly, our results provide a roadmap for an actionable DLBCL classification.
Details
- Title: Subtitle
- Molecular subtypes of diffuse large B cell lymphoma are associated with distinct pathogenic mechanisms and outcomes
- Creators
- Bjoern Chapuy - Harvard UniversityChip Stewart - Broad InstituteAndrew J Dunford - Broad InstituteJaegil Kim - Broad InstituteAtanas Kamburov - Broad InstituteRobert A Redd - Dana-Farber Cancer InstituteMike S Lawrence - Massachusetts General HospitalMargaretha G M Roemer - Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USAAmy J Li - Boston UniversityMarita Ziepert - Institute for Medical Informatics, Statistics and Epidemiology, University Leipzig, Leipzig, GermanyAnnette M Staiger - Robert Bosch HospitalJeremiah A Wala - Broad InstituteMatthew D Ducar - Dana-Farber Cancer InstituteIgnaty Leshchiner - Broad InstituteEster Rheinbay - Broad InstituteAmaro Taylor-Weiner - Broad InstituteCaroline A Coughlin - Dana-Farber Cancer InstituteJulian M Hess - Broad InstituteChandra S Pedamallu - Broad InstituteDimitri Livitz - Broad InstituteDaniel Rosebrock - Broad InstituteMara Rosenberg - Broad InstituteAdam A Tracy - Broad InstituteHeike Horn - University of TübingenPaul van Hummelen - Dana-Farber Cancer InstituteAndrew L Feldman - Mayo CLinic, Rochester, MN, USA,Brian K Link - University of IowaAnne J Novak - Mayo ClinicJames R Cerhan - Mayo ClinicThomas M Habermann - Mayo ClinicReiner Siebert - Universität UlmAndreas Rosenwald - University of WürzburgAaron R Thorner - Dana-Farber Cancer InstituteMatthew L Meyerson - Broad InstituteTodd R Golub - Broad InstituteRameen Beroukhim - Broad InstituteGerald G Wulf - University of GöttingenGerman Ott - Robert Bosch HospitalScott J Rodig - Brigham and Women's HospitalStefano Monti - Boston UniversityDonna S Neuberg - Harvard UniversityMarkus Loeffler - Institute for Medical Informatics, Statistics and Epidemiology, University Leipzig, Leipzig, GermanyMichael Pfreundschuh - Saarland UniversityLorenz Trümper - University of GöttingenGad Getz - Broad InstituteMargaret A Shipp - Harvard University
- Resource Type
- Journal article
- Publication Details
- Nature medicine, Vol.24(5), pp.679-690
- DOI
- 10.1038/s41591-018-0016-8
- PMID
- 29713087
- PMCID
- PMC6613387
- NLM abbreviation
- Nat Med
- ISSN
- 1078-8956
- eISSN
- 1546-170X
- Grant note
- P01 CA163222 / NCI NIH HHS R01 CA155010 / NCI NIH HHS U24 CA210999 / NCI NIH HHS T32 HG002295 / NHGRI NIH HHS P30 CA086862 / NCI NIH HHS U54 HG003067 / NHGRI NIH HHS U24 CA143845 / NCI NIH HHS P50 CA097274 / NCI NIH HHS
- Language
- English
- Date published
- 05/2018
- Academic Unit
- Hematology, Oncology, and Blood & Marrow Transplantation; Epidemiology; Internal Medicine
- Record Identifier
- 9984359813202771
Metrics
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