ANALYSIS OF ABNORMAL GENES ASSOCIATED WITH SYNOVIAL SARCOMA ONCOGENESIS.

与滑膜肉瘤癌发生相关的异常基因分析。

基本信息

批准号：
11670185
负责人：
INAGAKI Hiroshi
金额：
$ 1.34万
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：
1999
资助国家：
日本
起止时间：
1999 至 2000
项目状态：
已结题

项目摘要

Chromosome translocation t (X ; 18)(p11.2 ; q11.2) has been detected in more than 95% of the synovial sarcomas. The proximal portion of the SYT gene at 18q11 is fused the distal portion of one of two duplicated genes atXp11, SSX1 and SSX2. This SYT-SSX chimeric gene is considered to be closely associated with synovial sarcoma oncogenesis. Detection of this chimeric gene is useful in pathological diagnosis of synovial sarcoma. We extracted RNA from routinely-processed cytological and histological specimens of synovial sarcoma cases and detected SYT-SSX chimeric transcript in more than 90% of the cases using highly sensitive RT-PCR.In the next step, we studied the clinicopathological significance of the SSX type involved in the SYT-SSX fusion. Synovial sarcoma cases that had no distant metastasis at surgery were included. The SSX type involved in each case was confirmed, then, histological type, mitotic figures, prognosis, and expression of following proteins were investigated ; cell cycle-associated proteins, Ki67 and p27, and apoptosis-associated proteins, p53 and bcl-2. SYT-SSX1 fusion was associated with high expression of Ki67 and increased mitotic figures, but not with other factors. Clinically, SYT-SSX1, mitotic figures, and Ki67 expression were important factors for worse disease-free survival. We are interested in the mechanism by which SYT-SSX fusion proteins promote cell proliferation. Bacause SYT-SSX fusion protein does not possess apparent DNA-or RNA-binding domains, the fusion protein may bind to unknown proteins that would regulate cell cycling. We have found some candidate proteins by Two-hybrid system using SYT-SSX fusion gene transfection into yeast, and are studying the significance of these proteins in synovial sarcoma oncogenesis.

在超过95％的滑膜肉瘤中检测到了染色体易位T（X; 18）（P11.2; Q11.2）。 18Q11 SYT基因的近端部分融合了两个重复基因ATXP11，SSX1和SSX2之一的远端部分。该SYT-SSX嵌合基因被认为与滑膜肉瘤的肿瘤发生密切相关。该嵌合基因的检测可用于滑膜肉瘤的病理诊断。我们从下一步使用高度敏感的RT-PCR.中从90％以上的病例中检测到了通常处理的细胞学和组织学标本的RNA，并在下一步中研究了SSXSX的临床病理学意义。涉及SYT-SSX融合的类型。包括手术时没有远处转移的滑膜肉瘤病例。确认了每种情况中涉及的SSX类型，然后研究了组织学类型，有丝分裂图，预后和以下蛋白质的表达。细胞周期相关蛋白，Ki67和P27，以及与凋亡相关的蛋白，p53和Bcl-2。 SYT-SSX1融合与Ki67的高表达和有丝分裂数字增加有关，但与其他因素无关。在临床上，SYT-SSX1，有丝分裂图和Ki67表达是较差的无病生存率的重要因素。我们对SYT-SSX融合蛋白促进细胞增殖的机制感兴趣。 BACAUSE SYT-SSX融合蛋白不具有明显的DNA-或RNA结合结构域，融合蛋白可能与未知的蛋白结合，该蛋白会调节细胞循环。我们使用SYT-SSX融合基因转染到酵母中发现了一些候选蛋白，并正在研究这些蛋白在滑膜肉瘤肿瘤中的重要性。