Abstract
Gastrointestinal (g.i.) large cell lymphoma is currently regarded as diffuse large B-cell lymphoma (DLBCL) despite a more favorable clinical outcome compared to other DLBCL. Cluster analyses on a transcriptome signature of NF-κB target genes of 30 g.i. marginal zone B-cell lymphomas (MZBL; 8 g.i. MZBL, 22 large cell MZBL - among them 9 with coexisting small cell component) and 6 DLBCL (3 activated B-cell like (ABC), 3 germinal center-like (GCB)) reveals a distinct pattern. The distinctiveness of large cell MZBL samples is further confirmed by a cohort of 270 available B-cell lymphoma and B-cell in silico profiles. Of the NF-κB genes analyzed, c-REL was overexpressed in g.i. MZBL. c-REL amplification was limited to 6/22 large cell MZBL including the large cell component of 2/9 composite small cell/large cell lymphomas, and c-Rel protein expression was found in the large cell compartment of composite lymphomas. Classification experiments on DLBCL and large cell MZBL profiles support the concept that the large cell MZBL is a distinct type of B-cell lymphoma.
Highlights
Marginal zone B-cell lymphoma (MZBL) of the mucosa-associated lymphoid tissue (MALT) is an indolent neoplasm with a typical small cell morphology[1]
We found that c-REL copies in terms of high-level amplifications were limited to 6/18 large cell marginal zone B-cell lymphomas (MZBL) samples
We show in a transcriptomic approach that in a small cohort of B-cell lymphoma, diffuse large B-cell lymphoma (DLBCL), large cell MZBL, and g.i
Summary
Marginal zone B-cell lymphoma (MZBL) of the mucosa-associated lymphoid tissue (MALT) is an indolent neoplasm with a typical small cell morphology[1]. We showed previously that the morphologically different parts of ComL are clonally related, and demonstrated that the large cell parts are blastically transformed g.i. tract MZBL8–11 In this follow-up study, we investigate whether the pathogenesis of g.i. large cell MZBL translates into an expression signature distinct from those of other DLBCL. Relabelling experiments are used to prove identified groups Such experiments were performed in order to analyze whether or not MZBL is a learnable and discriminable subtype of DLBCLs besides the activated B-cell like (ABC) and the germinal center B-cell like (GCB)[13,14,15]. We conclude that large cell MZBL is a separate group distinctive of conventional DLBCL
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