A20deletion is associated with copy number gain at theTNFA/B/Clocus and occurs preferentially in translocation-negative MALT lymphoma of the ocular adnexa and salivary glands


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Abstract

The genetic basis of MALT lymphoma is largely unknown. Characteristic chromosomal translocations are frequently associated with gastric and pulmonary cases, but are rare at other sites. We compared the genetic profiles of 33 ocular adnexal and 25 pulmonary MALT lymphomas by 1 Mb array–comparative genomic hybridization (CGH) and revealed recurrent 6q23 losses and 6p21.2–6p22.1 gains exclusive to ocular cases. High-resolution chromosome 6 tile-path array–CGH identified NF-κB inhibitorA20as the target of 6q23.3 deletion andTNFA/B/Clocus as a putative target of 6p21.2–22.1 gain. Interphase fluorescencein situhybridization showed thatA20deletion occurred in MALT lymphoma of the ocular adnexa (8/42 = 19%), salivary gland (2/24 = 8%), thyroid (1/9 = 11%) and liver (1/2), but not in the lung (26), stomach (45) and skin (13). Homozygous deletion was observed in three cases.A20deletion andTNFA/B/Cgain were significantly associated (p< 0.001) and exclusively found in cases without characteristic translocation. In ocular cases,A20deletion was associated with concurrent involvement of different adnexal tissues or extraocular sites at diagnosis (p= 0.007), a higher proportion of relapse (67% versus 37%) and a shorter relapse-free survival (p= 0.033).A20deletion and gain atTNFA/B/Clocus may thus play an important role in the development of translocation-negative MALT lymphoma. Copyright © 2008 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

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