Genetic subdivisions of follicular lymphoma defined by distinct coding and noncoding mutation patterns.

Autor:	Dreval K; Canada's Michael Smith Genome Sciences Centre, BC Cancer, Vancouver, BC, Canada.; Department of Molecular Biology and Biochemistry, Simon Fraser University, Burnaby, BC, Canada., Hilton LK; Centre for Lymphoid Cancer, BC Cancer, Vancouver, BC, Canada., Cruz M; Department of Molecular Biology and Biochemistry, Simon Fraser University, Burnaby, BC, Canada., Shaalan H; Department of Molecular Biology and Biochemistry, Simon Fraser University, Burnaby, BC, Canada., Ben-Neriah S; Centre for Lymphoid Cancer, BC Cancer, Vancouver, BC, Canada., Boyle M; Centre for Lymphoid Cancer, BC Cancer, Vancouver, BC, Canada., Collinge B; Centre for Lymphoid Cancer, BC Cancer, Vancouver, BC, Canada., Coyle KM; Department of Molecular Biology and Biochemistry, Simon Fraser University, Burnaby, BC, Canada., Duns G; Centre for Lymphoid Cancer, BC Cancer, Vancouver, BC, Canada., Farinha P; Centre for Lymphoid Cancer, BC Cancer, Vancouver, BC, Canada., Grande BM; Sage Bionetworks, Seattle, WA., Meissner B; Centre for Lymphoid Cancer, BC Cancer, Vancouver, BC, Canada., Pararajalingam P; Department of Molecular Biology and Biochemistry, Simon Fraser University, Burnaby, BC, Canada., Rushton CK; Department of Molecular Biology and Biochemistry, Simon Fraser University, Burnaby, BC, Canada., Slack GW; Centre for Lymphoid Cancer, BC Cancer, Vancouver, BC, Canada., Wong J; Centre for Lymphoid Cancer, BC Cancer, Vancouver, BC, Canada., Mungall AJ; Canada's Michael Smith Genome Sciences Centre, BC Cancer, Vancouver, BC, Canada., Marra MA; Canada's Michael Smith Genome Sciences Centre, BC Cancer, Vancouver, BC, Canada., Connors JM; Centre for Lymphoid Cancer, BC Cancer, Vancouver, BC, Canada., Steidl C; Centre for Lymphoid Cancer, BC Cancer, Vancouver, BC, Canada., Scott DW; Centre for Lymphoid Cancer, BC Cancer, Vancouver, BC, Canada., Morin RD; Canada's Michael Smith Genome Sciences Centre, BC Cancer, Vancouver, BC, Canada.; Department of Molecular Biology and Biochemistry, Simon Fraser University, Burnaby, BC, Canada.
Jazyk:	angličtina
Zdroj:	Blood [Blood] 2023 Aug 10; Vol. 142 (6), pp. 561-573.
DOI:	10.1182/blood.2022018719
Abstrakt:	Follicular lymphoma (FL) accounts for ∼20% of all new lymphoma cases. Increases in cytological grade are a feature of the clinical progression of this malignancy, and eventual histologic transformation (HT) to the aggressive diffuse large B-cell lymphoma (DLBCL) occurs in up to 15% of patients. Clinical or genetic features to predict the risk and timing of HT have not been described comprehensively. In this study, we analyzed whole-genome sequencing data from 423 patients to compare the protein coding and noncoding mutation landscapes of untransformed FL, transformed FL, and de novo DLBCL. This revealed 2 genetically distinct subgroups of FL, which we have named DLBCL-like (dFL) and constrained FL (cFL). Each subgroup has distinguishing mutational patterns, aberrant somatic hypermutation rates, and biological and clinical characteristics. We implemented a machine learning-derived classification approach to stratify patients with FL into cFL and dFL subgroups based on their genomic features. Using separate validation cohorts, we demonstrate that cFL status, whether assigned with this full classifier or a single-gene approximation, is associated with a reduced rate of HT. This implies distinct biological features of cFL that constrain its evolution, and we highlight the potential for this classification to predict HT from genetic features present at diagnosis. (© 2023 by The American Society of Hematology. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved.)
Databáze:	MEDLINE
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