Alternative splicing discriminates molecular subtypes and has prognostic impact in diffuse large B-cell lymphoma

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Leivonen , S-K , Taskinen , M , Cervera , A , Karjalainen-Lindsberg , M-L , Delabie , J , Holte , H , Lehtonen , R , Hautaniemi , S & Leppa , S 2017 , ' Alternative splicing discriminates molecular subtypes and has prognostic impact in diffuse large B-cell lymphoma ' , Blood cancer journal , vol. 7 , 596 . https://doi.org/10.1038/bcj.2017.71

Title: Alternative splicing discriminates molecular subtypes and has prognostic impact in diffuse large B-cell lymphoma
Author: Leivonen, S-K; Taskinen, M.; Cervera, A.; Karjalainen-Lindsberg, M-L; Delabie, J.; Holte, H.; Lehtonen, R.; Hautaniemi, S.; Leppa, S.
Contributor: University of Helsinki, Research Programs Unit
University of Helsinki, Research Programs Unit
University of Helsinki, Research Programs Unit
University of Helsinki, Medicum
University of Helsinki, Research Programs Unit
University of Helsinki, Medicum
University of Helsinki, Clinicum
Date: 2017-08-25
Language: eng
Number of pages: 10
Belongs to series: Blood cancer journal
ISSN: 2044-5385
URI: http://hdl.handle.net/10138/224355
Abstract: Effect of alternative splicing (AS) on diffuse large B-cell lymphoma (DLBCL) pathogenesis and survival has not been systematically addressed. Here, we compared differentially expressed genes and exons in association with survival after chemoimmunotherapy, and between germinal center B-cell like (GCB) and activated B-cell like (ABC) DLBCLs. Genome-wide exon array-based screen was performed from samples of 38 clinically high-risk patients who were treated in a Nordic phase II study with dose-dense chemoimmunotherapy and central nervous system prophylaxis. The exon expression profile separated the patients according to molecular subgroups and survival better than the gene expression profile. Pathway analyses revealed enrichment of AS genes in inflammation and adhesion-related processes, and in signal transduction, such as phosphatidylinositol signaling system and adenosine triphosphate binding cassette transporters. Altogether, 49% of AS-related exons were protein coding, and domain prediction showed 28% of such exons to include a functional domain, such as transmembrane helix domain or phosphorylation sites. Validation in an independent cohort of 92 DLBCL samples subjected to RNA-sequencing confirmed differential exon usage of selected genes and association of AS with molecular subtypes and survival. The results indicate that AS events are able to discriminate GCB and ABC DLBCLs and have prognostic impact in DLBCL.
Subject: ACUTE LYMPHOBLASTIC-LEUKEMIA
CHEMOTHERAPY PLUS RITUXIMAB
CD44 VARIANT ISOFORMS
CLINICAL ONCOLOGY
HODGKIN-LYMPHOMA
EXPRESSION
PROTEIN
CANCER
SURVIVAL
DLBCL
3122 Cancers
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