Significant association between TNFAIP3 inactivation and biased immunoglobulin heavy chain variable region 4-34 usage in mucosa-associated lymphoid tissue lymphoma

Publication

Significant association between TNFAIP3 inactivation and biased immunoglobulin heavy chain variable region 4-34 usage in mucosa-associated lymphoid tissue lymphoma

Journal Paper/Review - Aug 7, 2017

Moody Sarah, Bi Yingwen, Raderer Markus, Ashton-Key Margaret, Goodlad John, Liu Hongxiang, Cogliatti Sergio B., Chuang Shih-Sung, Robson Alistair, Zeng Naiyan, Xue Xuemin, Dunn-Walters Deborah, Ochoa Ruiz Eguzkine, Clipson Alexandra, Wang Ming, Escudero-Ibarz Leire, Du Ming-Qing

Citation

Moody S, Bi Y, Raderer M, Ashton-Key M, Goodlad J, Liu H, Cogliatti S, Chuang S, Robson A, Zeng N, Xue X, Dunn-Walters D, Ochoa Ruiz E, Clipson A, Wang M, Escudero-Ibarz L, Du M. Significant association between TNFAIP3 inactivation and biased immunoglobulin heavy chain variable region 4-34 usage in mucosa-associated lymphoid tissue lymphoma. J Pathol 2017; 243:3-8.

Type

Journal Paper/Review (English)

Journal

J Pathol 2017; 243

Publication Date

Aug 7, 2017

Issn Electronic

1096-9896

Pages

3-8

Brief description/objective

Both antigenic drive and genetic change play critical roles in the development of mucosa-associated lymphoid tissue (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 immunoglobulin heavy chain variable region (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 nuclear factor-κB (NF-κB) pathway] in ocular adnexal MALT lymphoma; (2) IGHV1-69 was significantly overrepresented (54%) in MALT lymphoma of the salivary gland, but was not associated with mutation in any of the 17 genes investigated; and (3) MALT lymphoma lacked mutations that are frequently seen in other B-cell lymphomas characterized by constitutive NF-κB activities, including mutations in 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-κB regulators in MALT lymphoma, arguing for their cooperation in sustaining chronic B-cell receptor signalling and driving oncogenesis in lymphoma development. Copyright © 2017 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.