Barış İkbal Cansu, Caner Vildan, Şen Türk Nilay, Sarı İsmail, Hacıoğlu Sibel, Doğu Mehmet Hilmi, Çetin Ozan, Tepeli Emre, Can Özge, Bağcı Gülseren, Keskin Ali
Pamukkale University Faculty of Medicine, Department of Medical Biology, Denizli, Turkey Phone: +90 258 296 24 94 E-mail:
Turk J Haematol. 2015 Dec;32(4):295-303. doi: 10.4274/tjh.2014.0174. Epub 2015 Apr 27.
Diffuse large B-cell lymphoma (DLBCL) is the most common type of non-Hodgkin lymphoma among adults and is characterized by heterogeneous clinical, immunophenotypic, and genetic features. Different mechanisms deregulating cell cycle and apoptosis play a role in the pathogenesis of DLBCL. Growth arrest DNA damage-inducible 45 (GADD45γ) is an important gene family involved in these mechanisms. The aims of this study are to determine the frequency of GADD45γ methylation, to evaluate the correlation between GADD45γ methylation and protein expression, and to investigate the relation between methylation status and clinicopathologic parameters in DLBCL tissues and reactive lymphoid node tissues from patients with reactive lymphoid hyperplasia.
Thirty-six tissue samples of DLBCL and 40 nonmalignant reactive lymphoid node tissues were analyzed in this study. Methylation-sensitive high-resolution melting analysis was used for the determination of GADD45γ methylation status. The GADD45γ protein expression was determined by immunohistochemistry.
GADD45γ methylation was frequent (50.0%) in DLBCL. It was also significantly higher in advanced-stage tumors compared with early-stage (p=0.041). In contrast, unmethylated GADD45γ was associated with nodal involvement as the primary anatomical site (p=0.040).
The results of this study show that, in contrast to solid tumors, the frequency of GADD45γ methylation is higher and this epigenetic alteration of GADD45γ may be associated with progression in DLBCL. In addition, nodal involvement is more likely to be present in patients with unmethylated GADD45γ.
弥漫性大B细胞淋巴瘤（DLBCL）是成人非霍奇金淋巴瘤最常见的类型，具有异质性的临床、免疫表型和基因特征。不同的细胞周期和凋亡失调机制在DLBCL的发病机制中起作用。生长停滞DNA损伤诱导蛋白45（GADD45γ）是参与这些机制的一个重要基因家族。本研究的目的是确定GADD45γ甲基化的频率，评估GADD45γ甲基化与蛋白表达之间的相关性，并研究DLBCL组织和反应性淋巴增生患者反应性淋巴结组织中甲基化状态与临床病理参数之间的关系。
本研究分析了36例DLBCL组织样本和40例非恶性反应性淋巴结组织。采用甲基化敏感的高分辨率熔解分析来确定GADD45γ甲基化状态。通过免疫组织化学测定GADD45γ蛋白表达。
GADD45γ甲基化在DLBCL中很常见（50.0%）。与早期肿瘤相比，晚期肿瘤中的甲基化也显著更高（p=0.041）。相反，未甲基化的GADD45γ与以淋巴结受累作为主要解剖部位相关（p=0.040）。
本研究结果表明，与实体瘤不同，GADD45γ甲基化的频率更高，这种GADD45γ的表观遗传改变可能与DLBCL的进展相关。此外，GADD45γ未甲基化的患者更可能出现淋巴结受累。
