Division of Molecular Histopathology, Department of Pathology, University of Cambridge, Addenbrooke's Hospital, Cambridge CB2 2QQ, UK.
Haematologica. 2012 Jun;97(6):926-30. doi: 10.3324/haematol.2010.036798. Epub 2011 Dec 29.
Recent studies showed A20 inactivation by deletion, mutation and promoter methylation in ocular adnexal mucosa-associated lymphoid tissue lymphoma. However, the incidences of A20 abnormalities and their clinical impact remain for the most part unknown. It is also unknown whether ABIN-1 and ABIN-2, the components of the A20 NF-κB inhibitor complex, are inactivated by genetic changes in ocular adnexal mucosa-associated lymphoid tissue lymphoma. A total of 105 cases were investigated for A20 mutation/deletion, ABIN-1/2 mutation, MALT1 and IGH involved translocation. Somatic mutation was seen frequently in A20 (28.6%) but rarely in ABIN-1 (1%) and ABIN-2 (1%). A20 mutations were significantly associated with A20 heterozygous deletion, and both were mutually exclusive from the MALT1 or IGH involved translocations. A20 mutation/deletion was also significantly associated with increased expression of the NF-κB target genes CCR2, TLR6 and BCL2. The cases with A20 mutation/deletion required significantly higher radiation dosages to achieve complete remission than those without these abnormalities.
最近的研究表明，眼附属器黏膜相关淋巴组织淋巴瘤中存在 A20 的缺失、突变和启动子甲基化导致的失活。然而，A20 异常的发生率及其临床影响在很大程度上仍然未知。A20 NF-κB 抑制剂复合物的组成部分 ABIN-1 和 ABIN-2 是否因遗传变化而失活，目前也尚不清楚。共对 105 例病例进行了 A20 突变/缺失、ABIN-1/2 突变、MALT1 和 IGH 相关易位的检测。体细胞突变在 A20 中很常见（28.6%），但在 ABIN-1（1%）和 ABIN-2（1%）中很少见。A20 突变与 A20 杂合性缺失显著相关，且两者均与 MALT1 或 IGH 相关易位相互排斥。A20 突变/缺失也与 NF-κB 靶基因 CCR2、TLR6 和 BCL2 的表达增加显著相关。发生 A20 突变/缺失的病例需要更高的放射剂量才能达到完全缓解，而没有这些异常的病例则不需要。
