Distinct subtypes of diffuse large B-cell lymphoma defined by hypermutated genes

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Alkodsi , A , Cervera , A , Zhang , K , Louhimo , R , Meriranta , L , Pasanen , A , Leivonen , S-K , Holte , H , Leppä , S , Lehtonen , R & Hautaniemi , S 2019 , ' Distinct subtypes of diffuse large B-cell lymphoma defined by hypermutated genes ' , Leukemia , vol. 33 , no. 11 , pp. 2662-2672 . https://doi.org/10.1038/s41375-019-0509-6

Title: Distinct subtypes of diffuse large B-cell lymphoma defined by hypermutated genes
Author: Alkodsi, Amjad; Cervera, Alejandra; Zhang, Kaiyang; Louhimo, Riku; Meriranta, Leo; Pasanen, Annika; Leivonen, Suvi-Katri; Holte, Harald; Leppä, Sirpa; Lehtonen, Rainer; Hautaniemi, Sampsa
Contributor organization: Sampsa Hautaniemi / Principal Investigator
Research Programs Unit
Research Program in Systems Oncology
Faculty of Medicine
University of Helsinki
ATG - Applied Tumor Genomics
HUS Comprehensive Cancer Center
Department of Oncology
University Management
Department of Biochemistry and Developmental Biology
Date: 2019-11
Language: eng
Number of pages: 11
Belongs to series: Leukemia
ISSN: 0887-6924
DOI: https://doi.org/10.1038/s41375-019-0509-6
URI: http://hdl.handle.net/10138/314705
Abstract: Diffuse large B-cell lymphoma (DLBCL) is a biologically and clinically heterogeneous disease whose personalized clinical management requires robust molecular stratification. Here, we show that somatic hypermutation (SHM) patterns constitute a marker for DLBCL molecular classification. The activity of SHM mutational processes delineated the cell of origin (COO) in DLBCL. Expression of the herein identified 36 SHM target genes stratified DLBCL into four novel SHM subtypes. In a meta-analysis of patients with DLBCL treated with immunochemotherapy, the SHM subtypes were significantly associated with overall survival (1642 patients) and progression-free survival (795 patients). Multivariate analysis of survival indicated that the prognostic impact of the SHM subtypes is independent from the COO classification and the International Prognostic Index. Furthermore, the SHM subtypes had a distinct clinical outcome within each of the COO subtypes, and strikingly, even within unclassified DLBCL. The genetic landscape of the four SHM subtypes indicated unique associations with driver alterations and oncogenic signaling in DLBCL, which suggests a possibility for therapeutic exploitation. These findings provide a biologically driven classification system in DLBCL with potential clinical applications.
3122 Cancers
Peer reviewed: Yes
Usage restriction: openAccess
Self-archived version: acceptedVersion

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