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Molecular subsets of mantle cell lymphoma defined by the IGHV mutational status and SOX11 expression have distinct biologic and clinical features.

Abstract：

:Mantle cell lymphoma (MCL) is a heterogeneous disease with most patients following an aggressive clinical course, whereas others having an indolent behavior. We conducted an integrative and multidisciplinary analysis of 177 MCL to determine whether the immunogenetic features of the clonotypic B-cell receptors (BcR) may identify different subsets of tumors. Truly unmutated (100% identity) IGHV genes were found in 24% cases, 40% were minimally/borderline mutated (99.9%-97%), 19% significantly mutated (96.9%-95%), and 17% hypermutated (<95%). Tumors with high or low mutational load used different IGHV genes, and their gene expression profiles were also different for several gene pathways. A gene set enrichment analysis showed that MCL with high and low IGHV mutations were enriched in memory and naive B-cell signatures, respectively. Furthermore, the highly mutated tumors had less genomic complexity, were preferentially SOX11-negative, and showed more frequent nonnodal disease. The best cut-off of germline identity of IGHV genes to predict survival was 97%. Patients with high and low mutational load had significant different outcome with 5-year overall survival (OS) of 59% and 40%, respectively (P = 0.004). Nodal presentation and SOX11 expression also predicted for poor OS. In a multivariate analysis, IGHV gene status and SOX11 expression were independent risk factors. In conclusion, these observations suggest the idea that MCL with mutated IGHV, SOX11-negativity, and nonnodal presentation correspond to a subtype of the disease with more indolent behavior.

journal_name

Cancer Res

journal_title

Cancer research

authors

Navarro A,Clot G,Royo C,Jares P,Hadzidimitriou A,Agathangelidis A,Bikos V,Darzentas N,Papadaki T,Salaverria I,Pinyol M,Puig X,Palomero J,Vegliante MC,Amador V,Martinez-Trillos A,Stefancikova L,Wiestner A,Wilson W,Po

doi

10.1158/0008-5472.CAN-12-1615

subject

Has Abstract

pub_date

2012-10-15 00:00:00

pages

5307-16

issue

eissn

0008-5472

issn

1538-7445

pii

0008-5472.CAN-12-1615

journal_volume

pub_type

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Molecular subsets of mantle cell lymphoma defined by the IGHV mutational status and SOX11 expression have distinct biologic and clinical features.