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KLF2 mutation is the most frequent somatic change in splenic marginal zone lymphoma and identifies a subset with distinct genotype.

Abstract：

:To characterise the genetics of splenic marginal zone lymphoma (SMZL), we performed whole exome sequencing of 16 cases and identified novel recurrent inactivating mutations in Kruppel-like factor 2 (KLF2), a gene whose deficiency was previously shown to cause splenic marginal zone hyperplasia in mice. KLF2 mutation was found in 40 (42%) of 96 SMZLs, but rarely in other B-cell lymphomas. The majority of KLF2 mutations were frameshift indels or nonsense changes, with missense mutations clustered in the C-terminal zinc finger domains. Functional assays showed that these mutations inactivated the ability of KLF2 to suppress NF-κB activation by TLR, BCR, BAFFR and TNFR signalling. Further extensive investigations revealed common and distinct genetic changes between SMZL with and without KLF2 mutation. IGHV1-2 rearrangement and 7q deletion were primarily seen in SMZL with KLF2 mutation, while MYD88 and TP53 mutations were nearly exclusively found in those without KLF2 mutation. NOTCH2, TRAF3, TNFAIP3 and CARD11 mutations were observed in SMZL both with and without KLF2 mutation. Taken together, KLF2 mutation is the most common genetic change in SMZL and identifies a subset with a distinct genotype characterised by multi-genetic changes. These different genetic changes may deregulate various signalling pathways and generate cooperative oncogenic properties, thereby contributing to lymphomagenesis.

journal_name

Leukemia

journal_title

Leukemia

authors

Clipson A,Wang M,de Leval L,Ashton-Key M,Wotherspoon A,Vassiliou G,Bolli N,Grove C,Moody S,Escudero-Ibarz L,Gundem G,Brugger K,Xue X,Mi E,Bench A,Scott M,Liu H,Follows G,Robles EF,Martinez-Climent JA,Oscier D,Wa

doi

10.1038/leu.2014.330

subject

Has Abstract

pub_date

2015-05-01 00:00:00

pages

1177-85

issue

5

eissn

0887-6924

issn

1476-5551

pii

leu2014330

journal_volume

29

pub_type

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