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Significant association between TNFAIP3 inactivation and biased IGHV4-34 usage in MALT lymphoma

Moody, Sarah, Escudero-Ibarz, Leire, Wang, Ming, Clipson, Alexandra, Ochoa Ruiz, Eguzkine, Dunn-Walters, Deborah, Xue, Xuemin, Zeng, Naiyan, Robson, Alistair, Chuang, Shih-Sung , Cogliatti, Sergio, Liu, Hongxiang, Goodlad, John, Ashton-Key, Margaret, Raderer, Markus, Bi, Yingwen and Du, Ming-Qing (2017) Significant association between TNFAIP3 inactivation and biased IGHV4-34 usage in MALT lymphoma Journal of Pathology.

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Abstract

Both antigenic drive and genetic change play a critical role in the development of MALT lymphoma, but neither alone is sufficient for malignant transformation, and lymphoma development critically depends on their cooperation. However, which of these different events concur and how they cooperate in MALT lymphomagenesis is totally unknown. To explore this, we investigated somatic mutations of 17 genes and IGHV usage in 179 MALT lymphomas from various sites. We showed that: 1) there was a significant association between the biased usage of IGHV4-34 (binds to the carbohydrate I/i antigens) and inactivating mutation of TNFAIP3 (encoding a global negative regulator of the canonical NF-B pathway) in ocular adnexal MALT lymphoma; 2) IGHV1-69 was significantly overrepresented (54%) in MALT lymphoma of salivary gland, but not associated with mutation in any of the 17 genes investigated; and 3) MALT lymphoma lacked mutations frequently seen in other B-cell lymphomas characterised by constitutive NF-B activities, including CD79B, CARD11, MYD88, TNFRSF11A and TRAF3. Our findings show for the first time a significant association between biased usage of autoreactive IGHV and somatic mutation of NF-B regulators in MALT lymphoma, arguing for their cooperation in sustaining chronic BCR signalling and driving oncogenesis in lymphoma development.

Item Type: Article
Divisions : Faculty of Health and Medical Sciences > School of Biosciences and Medicine
Authors :
NameEmailORCID
Moody, SarahUNSPECIFIEDUNSPECIFIED
Escudero-Ibarz, LeireUNSPECIFIEDUNSPECIFIED
Wang, MingUNSPECIFIEDUNSPECIFIED
Clipson, AlexandraUNSPECIFIEDUNSPECIFIED
Ochoa Ruiz, EguzkineUNSPECIFIEDUNSPECIFIED
Dunn-Walters, Deborahd.dunn-walters@surrey.ac.ukUNSPECIFIED
Xue, XueminUNSPECIFIEDUNSPECIFIED
Zeng, NaiyanUNSPECIFIEDUNSPECIFIED
Robson, AlistairUNSPECIFIEDUNSPECIFIED
Chuang, Shih-SungUNSPECIFIEDUNSPECIFIED
Cogliatti, SergioUNSPECIFIEDUNSPECIFIED
Liu, HongxiangUNSPECIFIEDUNSPECIFIED
Goodlad, JohnUNSPECIFIEDUNSPECIFIED
Ashton-Key, MargaretUNSPECIFIEDUNSPECIFIED
Raderer, MarkusUNSPECIFIEDUNSPECIFIED
Bi, YingwenUNSPECIFIEDUNSPECIFIED
Du, Ming-QingUNSPECIFIEDUNSPECIFIED
Date : 2017
Identification Number : 10.1002/path.4933
Copyright Disclaimer : © 2017 Pathological Society of Great Britain and Ireland
Depositing User : Clive Harris
Date Deposited : 29 Jun 2017 12:42
Last Modified : 17 Aug 2017 13:36
URI: http://epubs.surrey.ac.uk/id/eprint/841510

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