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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, 243 (1). pp. 3-8.

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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 :
Moody, Sarah
Escudero-Ibarz, Leire
Wang, Ming
Clipson, Alexandra
Ochoa Ruiz, Eguzkine
Xue, Xuemin
Zeng, Naiyan
Robson, Alistair
Chuang, Shih-Sung
Cogliatti, Sergio
Liu, Hongxiang
Goodlad, John
Ashton-Key, Margaret
Raderer, Markus
Bi, Yingwen
Du, Ming-Qing
Date : 7 August 2017
DOI : 10.1002/path.4933
Copyright Disclaimer : © 2017 Pathological Society of Great Britain and Ireland
Uncontrolled Keywords : MALT lymphoma; IGHV usage; TNFAIP3 mutation; NF-κB
Depositing User : Clive Harris
Date Deposited : 29 Jun 2017 12:42
Last Modified : 23 Jun 2018 02:08

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