日本東京大學研究人員在最新一期《自然》雜志網(wǎng)絡版上報告說，長期患胃炎等慢性炎癥是誘發(fā)部分惡性淋巴瘤的導火線,。
惡性淋巴瘤是承擔免疫功能的淋巴細胞癌變生成的,。東京大學研究人員開發(fā)出一種能高效檢測堿基排列個體差異的技術，并利用這項技術對約300名惡性淋巴瘤患者進行分析,。
結果顯示,，主要發(fā)生在消化道的“黏膜相關淋巴組織淋巴瘤”等惡性淋巴瘤患者中，約20％的人A20基因的堿基序列存在變異,，導致A20基因不能正常工作,。
A20基因在人體出現(xiàn)炎癥時發(fā)揮“剎車”作用，使得淋巴細胞不會無限增殖,。研究人員將A20基因不起作用的淋巴癌細胞移植到實驗鼠體內,，結果實驗鼠一旦出現(xiàn)炎癥，炎癥所產(chǎn)生的物質就會刺激淋巴癌細胞,，導致其異常增殖,，最后生成惡性淋巴瘤。
如果給實驗鼠植入A20基因不能正常工作的淋巴癌細胞,，但其體內沒有炎癥,，那么淋巴癌細胞就不會增殖。因此,，日本研究人員認為,，炎癥是誘發(fā)某些惡性淋巴瘤的導火線。（生物谷Bioon.com）
生物谷推薦原始出處：
Nature advance online publication 3 May 2009 | doi:10.1038/nature07969
Frequent inactivation of A20 in B-cell lymphomas
Motohiro Kato1,2, Masashi Sanada1,5, Itaru Kato6, Yasuharu Sato7, Junko Takita1,2,3, Kengo Takeuchi8, Akira Niwa6, Yuyan Chen1,2, Kumi Nakazaki1,4,5, Junko Nomoto9, Yoshitaka Asakura9, Satsuki Muto1, Azusa Tamura1, Mitsuru Iio1, Yoshiki Akatsuka11, Yasuhide Hayashi12, Hiraku Mori13, Takashi Igarashi2, Mineo Kurokawa4, Shigeru Chiba3, Shigeo Mori14, Yuichi Ishikawa8, Koji Okamoto10, Kensei Tobinai9, Hitoshi Nakagama10, Tatsutoshi Nakahata6, Tadashi Yoshino7, Yukio Kobayashi9 & Seishi Ogawa1,5
1 Cancer Genomics Project, Department of,
2 Pediatrics,
3 Cell Therapy and Transplantation Medicine, and,
4 Hematology and Oncology, Graduate School of Medicine, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan
5 Core Research for Evolutional Science and Technology, Japan Science and Technology Agency, 4-1-8, Honcho, Kawaguchi-shi, Saitama 332-0012, Japan
6 Department of Pediatrics, Graduate School of Medicine, Kyoto University, 54 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto 606-8507, Japan
7 Department of Pathology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 2-5-1 Shikata-cho, Kita-ku, Okayama 700-8558, Japan
8 Division of Pathology, The Cancer Institute of Japanese Foundation for Cancer Research, Japan, 3-10-6 Ariake, Koto-ku, Tokyo 135-8550, Japan
9 Hematology Division, Hospital, and,
10 Early Oncogenesis Research Project, Research Institute, National Cancer Center, 5-1-1 Tsukiji, Chuo-ku, Tokyo 104-0045, Japan
11 Division of Immunology, Aichi Cancer Center Research Institute, 1-1 Kanokoden, Chikusa-ku, Nagoya 464-8681, Japan
12 Gunma Children's Medical Center, 779 Shimohakoda, Hokkitsu-machi, Shibukawa 377-8577, Japan
13 Division of Hematology, Internal Medicine, Showa University Fujigaoka Hospital, 1-30, Fujigaoka, Aoba-ku, Yokohama-shi, Kanagawa 227-8501, Japan
14 Department of Pathology, Teikyo University School of Medicine, 2-11-1 Kaga, Itabashi-ku, Tokyo 173-8605, Japan
A20 is a negative regulator of the NF-B pathway and was initially identified as being rapidly induced after tumour-necrosis factor- stimulation1. It has a pivotal role in regulation of the immune response and prevents excessive activation of NF-B in response to a variety of external stimuli2, 3, 4, 5, 6, 7; recent genetic studies have disclosed putative associations of polymorphic A20 (also called TNFAIP3) alleles with autoimmune disease risk8, 9. However, the involvement of A20 in the development of human cancers is unknown. Here we show, using a genome-wide analysis of genetic lesions in 238 B-cell lymphomas, that A20 is a common genetic target in B-lineage lymphomas. A20 is frequently inactivated by somatic mutations and/or deletions in mucosa-associated tissue lymphoma (18 out of 87; 21.8%) and Hodgkin's lymphoma of nodular sclerosis histology (5 out of 15; 33.3%), and, to a lesser extent, in other B-lineage lymphomas. When re-expressed in a lymphoma-derived cell line with no functional A20 alleles, wild-type A20, but not mutant A20, resulted in suppression of cell growth and induction of apoptosis, accompanied by downregulation of NF-B activation. The A20-deficient cells stably generated tumours in immunodeficient mice, whereas the tumorigenicity was effectively suppressed by re-expression of A20. In A20-deficient cells, suppression of both cell growth and NF-B activity due to re-expression of A20 depended, at least partly, on cell-surface-receptor signalling, including the tumour-necrosis factor receptor. Considering the physiological function of A20 in the negative modulation of NF-B activation induced by multiple upstream stimuli, our findings indicate that uncontrolled signalling of NF-B caused by loss of A20 function is involved in the pathogenesis of subsets of B-lineage lymphomas.
