A20 IN MARGINAL ZONE LYMPHOMAS

Unique and shared cytogenetic abnormalities have been documented for marginal zone lymphomas (MZLs) arising at different sites. Recently, homozygous deletions of the chromosomal band 6q23, involving the tumor necrosis factor alpha-induced protein 3 (TNFAIP3, A20) gene, a negative regulator of NF-kappa B, were described in ocular adnexal MZL, suggesting a role for A20 as a tumor suppressor in this disease entity. Here, we investigated inactivation of A20 by DNA mutations or deletions in a panel of extranodal (EMZL), nodal (NMZL) and splenic (SMZL) MZLs. Inactivating mutations encoding truncated A20 proteins were identified in 6/32 (18.8%) MZLs, including 3/11 (27.3%) EMZLs, 2/9 (22.2%) NMZLs, and 1/12 (8.3%) SMZLs. Two additional unmutated non-splenic MZLs also showed mono- or biallelic A20 deletions by FISH and/or array-CGH. Thus, A20 loss by both somatic mutations and/or deletions represents a common genetic aberration across all MZL subtypes, which may contribute to lymphomagenesis by inducing constitutive NF-kappa B activation. Keywords: Genome variation profiling by SNP array 27 MZL samples. No technical replications.

已报道发生于不同部位的边缘区淋巴瘤（marginal zone lymphomas, MZLs）存在独特且共有的细胞遗传学异常。近期，有研究在眼附属器MZL中发现染色体区段6q23存在纯合缺失，该缺失区域涉及肿瘤坏死因子α诱导蛋白3（TNFAIP3, A20）基因——一种核因子κB（NF-κB）的负调控因子，这提示A20在该疾病亚型中发挥肿瘤抑制因子的作用。本研究针对一组结外（EMZL）、淋巴结（NMZL）及脾脏（SMZL）MZL样本，探究了A20基因通过DNA突变或缺失发生的失活情况。研究在6/32（18.8%）的MZL样本中检出了编码截短型A20蛋白的失活性突变，其中结外MZL为3/11（27.3%）、淋巴结MZL为2/9（22.2%）、脾脏MZL为1/12（8.3%）。另有2例未发生突变的非脾脏MZL样本，经荧光原位杂交（FISH）和/或阵列比较基因组杂交（array-CGH）检测，同样检出了单等位或双等位基因A20缺失。综上，体细胞突变与（或）缺失共同导致的A20缺失是所有MZL亚型中普遍存在的遗传学异常，其可通过诱导核因子κB持续性激活，进而参与淋巴瘤发生过程。关键词：基于SNP阵列的基因组变异谱分析、27例MZL样本、无技术重复。