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Genetic Abnormalities in MALT Lymphoma

MALT 淋巴瘤的遗传异常

基本信息

批准号：
17590311
负责人：
INAGAKI Hiroshi
金额：
$ 2.37万
依托单位：
NAGOYA CITY UNIVERSITY
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2005
资助国家：
日本
起止时间：
2005 至 2006
项目状态：
已结题

项目摘要

MALT lymphoma is generally associated with chronic inflammation. However, some tumors are independent of chronic inflammation, and positive for API2-MALT1 fusion gene. We performed the immunoglobulin heavy chain (IgH) gene analysis of gastric MALT lymphomas, and clarified that chronic inflammation-dependent tumors often used selected VH fragments, such as VH3-23 and VH3-30. In contrast, chronic inflammation-independent tumors used variegated VH fragments. This finding suggests that these two groups may be derived from different B-cell subsets, and progression from the former to the latter may not be a common pathway (Sakuma H, et al. Mod Pathol 2007). Thymic MALT lymphomas are closely associated with autoimmune disease. We analyzed these rare tumors for the IgH gene usage and found that they used VH fragments similar to those used in chronic inflammation-dependent gastric MALT lymphomas (Yoshida M, et al. J Pathol 2006). These data suggest that MALT lymphomas closely associated with ch … More ronic inflammation show restricted usage of VH fragments, and these tumors are genetically different from MALT lymphomas independent of chronic inflammation. Silencing of p16 gene has been associated with lymphoma progression. We analyzed p16 gene silencing in pulmonary MALT lymphomas and its clinicopathological significance. p16 gene was already silenced, mainly by gene hypermethylation, in many of the tumors at diagnosis, and this silencing was not correlated with any clinicopathological factors. This finding suggests that p16 gene silencing is associated with lymphomagenesis rather than lymphoma progression (Takino H, et al. Mod Pathol 2005). MALT lymphoma comprises up to 90% of primary pulmonary lymphomas, but its diagnosis is often difficult. API2-MALT1 fusion is specific to MALT lymphoma, and is detected in nearly half of the pulmonary cases. We performed a multiplex RT-PCR assay and successfully detected the fusion transcript using archival cytological specimens (BAL, sputum, and pleural effusion). Detection of API2-MALT1 fusion in these specimens would be useful as an ancillary assay for the diagnosis, staging, and follow-up of pulmonary MALT lymphoma (Inagaki H, et al. Int J Hematol 2005). We reported a case of oral MALT lymphoma that showed spontaneous regression (Sakuma H, et al. Pathol Int 2006), and cases that showed occurrence of diffuse large B-cell lymphomas after H. pylori eradication for MALT lymphomas (Iwano M, et al. Am J Gastroenterol 2006). Less

MALT淋巴瘤通常与慢性炎症相关。然而，有些肿瘤不依赖于慢性炎症，并且API 2-MALT 1融合基因阳性。我们对胃MALT淋巴瘤进行了免疫球蛋白重链（IgH）基因分析，并阐明慢性炎症依赖性肿瘤通常使用选定的VH片段，如VH 3 -23和VH 3 -30。相反，慢性炎症非依赖性肿瘤使用杂色VH片段。这一发现表明，这两组可能源自不同的B细胞亚群，从前者到后者的进展可能不是一个共同的途径（Sakuma H等人，Mod Pathol 2007）。胸腺MALT淋巴瘤与自身免疫性疾病密切相关。我们分析了这些罕见肿瘤的IgH基因使用情况，发现它们使用的VH片段与慢性炎症依赖性胃MALT淋巴瘤中使用的VH片段相似（Yoshida M，et al. J Pathol 2006）。这些数据表明，MALT淋巴瘤密切相关的ch ...更多信息慢性炎症显示VH片段的使用受限，并且这些肿瘤在遗传上不同于独立于慢性炎症的MALT淋巴瘤。p16基因的沉默与淋巴瘤的进展有关。我们分析了肺MALT淋巴瘤中p16基因沉默及其临床病理意义。p16基因在诊断时就已经沉默，主要是基因甲基化，这种沉默与任何临床病理因素无关。这一发现表明，p16基因沉默与淋巴瘤发生相关，而不是与淋巴瘤进展相关（Takino H，et al. Mod Pathol 2005）。MALT淋巴瘤包括高达90%的原发性肺淋巴瘤，但其诊断往往是困难的。API 2-MALT 1融合对MALT淋巴瘤具有特异性，并且在近一半的肺部病例中检测到。我们进行了多重RT-PCR检测，并成功地检测到融合转录档案细胞学标本（BAL，痰，胸腔积液）。在这些样本中检测API 2-MALT 1融合将可用作肺MALT淋巴瘤诊断、分期和随访的辅助测定（Inagaki H，et al. Int J Hematol 2005）。我们报告了1例口腔MALT淋巴瘤自发消退的病例（Sakuma H，et al. Pathol Int 2006），以及在H.幽门螺杆菌根除用于MALT淋巴瘤（Iwano M等人，Am J Gastroenterol 2006）。少