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

Détails

ID Serval
serval:BIB_A29AAB722678
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
KLF2 mutation is the most frequent somatic change in splenic marginal zone lymphoma and identifies a subset with distinct genotype.
Périodique
Leukemia
Auteur⸱e⸱s
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 E.F., Martinez-Climent J.A., Oscier D., Watkins A.J., Du M.Q.
ISSN
1476-5551 (Electronic)
ISSN-L
0887-6924
Statut éditorial
Publié
Date de publication
2015
Peer-reviewed
Oui
Volume
29
Numéro
5
Pages
1177-1185
Langue
anglais
Notes
Publication types: Journal Article Publication Status: ppublish
Résumé
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.
Pubmed
Web of science
Création de la notice
01/12/2014 10:06
Dernière modification de la notice
20/08/2019 16:08
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