Journal
CANCER CELL
Volume 37, Issue 4, Pages 551-+Publisher
CELL PRESS
DOI: 10.1016/j.ccell.2020.03.015
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Funding
- Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research from the National Cancer Institute [1P01CA229100]
- Terry Fox Research Institute [1061, 1043]
- NATIONAL CANCER INSTITUTE [ZIASC006741, ZIABC011354, ZIABC011006, ZIABC011007, ZIABC011999] Funding Source: NIH RePORTER
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The development of precision medicine approaches for diffuse large B cell lymphoma (DLBCL) is confounded by its pronounced genetic, phenotypic, and clinical heterogeneity. Recent multiplatform genomic studies revealed the existence of genetic subtypes of DLBCL using clustering methodologies. Here, we describe an algorithm that determines the probability that a patient's lymphoma belongs to one of seven genetic subtypes based on its genetic features. This classification reveals genetic similarities between these DLBCL subtypes and various indolent and extranodal lymphoma types, suggesting a shared pathogenesis. These genetic subtypes also have distinct gene expression profiles, immune microenvironments, and outcomes following immunochemotherapy. Functional analysis of genetic subtype models highlights distinct vulnerabilities to targeted therapy, supporting the use of this classification in precision medicine trials.
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