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© Research
Publication : Blood

Germline and somatic genetic variations of TNFAIP3 in lymphoma complicating primary Sjogren’s syndrome

Scientific Fields
Diseases
Organisms
Applications
Technique

Published in Blood - 24 Oct 2013

Nocturne G, Boudaoud S, Miceli-Richard C, Viengchareun S, Lazure T, Nititham J, Taylor KE, Ma A, Busato F, Melki J, Lessard CJ, Sivils KL, Dubost JJ, Hachulla E, Gottenberg JE, Lombès M, Tost J, Criswell LA, Mariette X

Link to Pubmed [PMID] – 24159176

Blood 2013 Dec;122(25):4068-76

Several autoimmune diseases, including primary Sjögren’s syndrome (pSS), are associated with an increased risk for lymphoma. Polymorphisms of TNFAIP3, which encodes the A20 protein that plays a key role in controlling nuclear factor κB activation, have been associated with several autoimmune diseases. Somatic mutations of TNFAIP3 have been observed in the mucosa-associated lymphoid tissue lymphoma subtype frequently associated with pSS. We studied germline and somatic abnormalities of TNFAIP3 in 574 patients with pSS, including 25 with lymphoma. Nineteen additional patients with pSS and lymphoma were available for exome sequence analysis. Functional abnormalities of A20 were assessed by gene reporter assays. The rs2230926 exonic variant was associated with an increased risk for pSS complicated by lymphoma (odds ratio, 3.36 [95% confidence interval, 1.34-8.42], and odds ratio, 3.26 [95% confidence interval, 1.31-8.12], vs controls and pSS patients without lymphoma, respectively; P = .011). Twelve (60%) of the 20 patients with paired germline and lymphoma TNFAIP3 sequence data had functional abnormalities of A20: 6 in germline DNA, 5 in lymphoma DNA, and 1 in both. The frequency was even higher (77%) among pSS patients with mucosa-associated lymphoid tissue lymphoma. Some of these variants showed impaired control of nuclear factor κB activation. These results support a key role for germline and somatic variations of A20 in the transformation between autoimmunity and lymphoma.

https://www.ncbi.nlm.nih.gov/pubmed/24159176