Molecular biologic, immunogenetic, and Epstein-Barr virus studies on nasal NK/T-cell lymphoma

鼻 NK/T 细胞淋巴瘤的分子生物学、免疫遗传学和 Epstein-Barr 病毒研究

• 批准号: 11470353
• 负责人: HARABUCHI Yasuaki
• 金额: $ 9.54万
• 依托单位: Asahikawa Medical College
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 1999
• 资助国家: 日本
• 起止时间: 1999 至 2001
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-11470353/
• 关键词: HEAD AND HECK MALIGNANCIES; NASAL T; NK-CELL LYMPHOMA; EPSTEIN-BARR VIRUS; IMMUNOLOGY; VIROLOGY; LMP-2A; P53癌抑制遺伝子

Mutations of p53 tumor suppressor gene, b-catenine gene, and ras gene, expressions of p53 protein and b-catenine, and clinical outcome were analyzed in 32 patients with nasal NK/T-Cell lymphoma. Of 32 patients, 6 mutations (2 silent and 4 missense) of p53 gene, 5 mutations (3 silent and 2 missense) of b-catenine gene, and each 1 mutation of N- and K-ras gene were detected. Overexpression of p53 parotein and b-catenine protein were found in 15 and 4 patients, respectively. The patients with mutations of these genes showed poor prognosis. Multivariate analysis revealed p53 gene muation as a most independent pronostic factor.Direct sequence analyzes for total region of LMP-1 and the exon 6 of LMP-2A in Epstein-Barr vius gene were performed using PCR-amplified products in 7 patients with nasal NK/T-cell lymphoma. A 30-bp deletion in the 3' C-terminal region of the LMP-1 gene was detected in all 7 samples. In the LMP-1 genes, 43 similar nucleotide changes were detected in all 7 patients and 11 sequence variations were found among 7 patients. With regard to the sequence of in exon 6 of LMP-2A gene, a similar nucleotide change (AGC to ACC, serine to threonine) at codon 348 was determined in all 7 patients.

分析32例鼻NK/T细胞淋巴瘤p53抑癌基因、b-catenine基因、ras基因突变、p53蛋白和b-catenine表达及临床预后。p53基因突变6例（2例沉默，4例错义），b-catenine基因突变5例（3例沉默，2例错义），N-ras和K-ras基因各1例。p53蛋白和b-连环蛋白分别在15例和4例患者中过度表达。这些基因突变的患者预后差。多因素分析显示p53基因突变是鼻NK/T细胞淋巴瘤最独立的易感因素。在所有7个样品中检测到LMP-1基因的3'C-末端区域中的30-bp缺失。在LMP-1基因中，7例患者共检测到43个相似的核苷酸变异，7例患者共检测到11个序列变异。7例患者LMP-2A基因外显子6的第348位密码子均发生了类似的碱基变化（AGC → ACC，丝氨酸→苏氨酸）。

项目成果

Ohsawa M., Shingu N., Inohara H., Kubo T., Yang Wl., Yoon JH., Aozasa K.: "Chronological changes in incidences of polymorphic reticulosis in Korea and Japan"Oncology. 56. 202-207 (1999)

Ohsawa M.、Shingu N.、Inohara H.、Kubo T.、Yang Wl.、Yoon JH.、Aozasa K.：“韩国和日本多形性网状细胞增多症发病率的时间变化”肿瘤学。

Hongyo T, Li T, Syaifudin M, Baslar R, Ikeda H, Kanakura Y, Aozasa K, Nomura T.: "Specific c-kit mutations in sinonasal natural killer/T-cell lymphoma in China and Japan"Cancer Res. 60・9. 2345-2347 (2000)

Hongyo T、Li T、Syafudin M、Baslar R、Ikeda H、Kanakura Y、Aozasa K、Nomura T.：“中国和日本鼻腔自然杀伤/T 细胞淋巴瘤的特定 c-kit 突变”Cancer Res 60。 9. 2345-2347 (2000)

Hongyo T., Li T., Syaifudin M., Baskar R., Ikeda H., Kanakura Y., Aozasa K., Nomura T.: "Specific c-kit mutations in sinonasal natural killer/T-cell lymphoma in China and Japan"Cancer Res.. 60. 2345-2347 (2000)

Hongyo T.、Li T.、Syafudin M.、Baskar R.、Ikeda H.、Kanakura Y.、Aozasa K.、Nomura T.：“中国和中国鼻窦自然杀伤/T 细胞淋巴瘤中的特定 c-kit 突变

原渕保明, 坂東伸幸, 荻野武, 山口治浩: "鼻腔原発悪性リンパ腫の臨床像とEBウイルス"ウイルス感染症セミナー. 2. 25-31 (2000)

Yasuaki Harabuchi、Nobuyuki Bando、Takeshi Ogino、Haruhiro Yamaguchi：“鼻腔原发性恶性淋巴瘤和 EB 病毒的临床特征”病毒感染研讨会。

Li T, Hongyo T, Syaifudin M, Nomura T, Dong Z, Shingu N, Kojya S, Nakatsuka S, Aozaka K: "Mutations of the p53 gene in nasal NK/T-cell lymphoma"Lab Invest. 80・4. 493-499 (2000)

Li T、Hongyo T、Syaifudin M、Nomura T、Dong Z、Shingu N、Kojya S、Nakatsuka S、Aozaka K：“鼻 NK/T 细胞淋巴瘤中 p53 基因的突变”Lab Invest 80・4。 -499 (2000)