Liu Fang, Karube Kennosuke, Kato Harumi, Arita Kotaro, Yoshida Noriaki, Yamamoto Kiyoko, Tsuzuki Shinobu, Kim Wonseog, Ko Young-Hyeh, Seto Masao
Division of Molecular Medicine, Aichi Cancer Center Research Institute, Nagoya, Japan.
Int J Clin Exp Pathol. 2012;5(5):436-41. Epub 2012 May 23.
Constitutive nuclear factor-kappa B (NF-κB) activation has been reported in ocular adnexal lymphoma (OAL). TNFAIP3/A20 is a "global" inhibitor of NF-κB pathway. We have shown that OAL has preferential loss of the 6q23.3 region where TNFAIP3/A20 exist, which is suggested to involve in lymphomagenesis of OAL. The mechanisms causing NF-κB activity in OAL remain elusive. Recently, NF-κB canonical pathway genes including CARD11, CD79B and MYD88 were shown to be frequently mutated in diffuse large B-cell lymphomas. In this study, we analyzed the mutation status of these genes by direct sequencing in 24 OAL cases including 9 cases with loss of 6q23.3 previously identified by array comparative genomic hybridization. We showed that genetic alterations of these genes were not found in OAL, a finding differing from that of most B-cell lymphomas. Genetic or epigenetic alterations in other genes are likely to be relevant in pathogenesis of OAL case without A20 loss.
据报道，眼部附属器淋巴瘤（OAL）中存在组成型核因子-κB（NF-κB）激活。TNFAIP3/A20是NF-κB通路的“全局”抑制剂。我们已经表明，OAL中存在TNFAIP3/A20的6q23.3区域存在优先缺失，这被认为与OAL的淋巴瘤发生有关。导致OAL中NF-κB活性的机制仍然不清楚。最近，包括CARD11、CD79B和MYD88在内的NF-κB经典通路基因在弥漫性大B细胞淋巴瘤中显示出频繁突变。在本研究中，我们通过直接测序分析了24例OAL病例中这些基因的突变状态，其中包括9例先前通过阵列比较基因组杂交鉴定出6q23.3缺失的病例。我们发现，在OAL中未发现这些基因的遗传改变，这一发现与大多数B细胞淋巴瘤不同。在没有A20缺失的OAL病例的发病机制中，其他基因的遗传或表观遗传改变可能与之相关。
