THE JAZF1 AND 2 GENES IN UTERINE SARCOMAS

子宫肉瘤中的 JAZF1 和 2 基因

• 批准号: 6377835
• 负责人: Jeffrey Sklar
• 金额: $ 30.29万
• 依托单位: BRIGHAM AND WOMEN'S HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-08-08 至 2005-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6377835
• 关键词: antisense nucleic acid; athymic mouse; chromosome translocation; complementary DNA; female; fusion gene; gene mutation; genetically modified animals; human tissue; microarray technology; neoplasm /cancer genetics; nucleic acid sequence; oligonucleotides; protein structure function; sarcoma; transcription factor; uterus neoplasms; women's health; yeast two hybrid system

DESCRIPTION: (Adapted from the investigator's abstract) Dr. Sklar has identified two previously unknown genes, termed JAZF1 and 2, which are fused in low grade endometrial stromal sarcomas (ESSs) as a consequence of a recurrent (7;17)(p15;q21) chromosomal translocation associated with these tumors. Both genes encode proteins containing zinc finger domains, and in JAZF1, the sequences of codons for two such domains closely resemble the sequence for two zinc fingers found in the transcription factor Sfplp, which has recently been implicated in the mechanism governing the G2/M checkpoint in the cell cycle of S. cervesiae. He proposes to characterize the JAZF1 and 2 genes in tumors and normal tissues through a series of studies, beginning with the completion of nucleotide sequence analysis of the amino terminal ends of the normal coding sequences, which have not yet been located. A wide variety of uterine and non-uterine sarcomas will be screened for the fusion transcript and mutations of the JAZF1 gene to determine the range of neoplasms containing abnormalities in the two genes and to answer a number of outstanding questions regarding the classification and histogenesis of uterine stromal tumors. Additionally, the ability of the JAZF1/JAZF2 fusion to induce malignant transformation will be investigated using both cultured cells and transgenic mice. Gene expression altered by the presence of the JAZF1/JAZF2 fusion will be analyzed by examining transcription profiles in cultured cells carry cDNA for the two genes transfected into bacteria. Interactions between the protein products of the two genes and other proteins will be explored using the yeast two-hybrid system. Phenotypic effects of the murine homologs for the JAZF1 and 2 will be assessed in knockout animals separately defective in both alleles. Finally, DNA binding sites for the two proteins will be sought and the sequences of these sites will be used in turn to identify genes transcriptionally regulated by JAZF1 and 2 in normal cells.

描述：（改编自研究者的摘要）Sklar 博士 鉴定出两个以前未知的基因，称为 JAZF1 和 2，它们融合在 由于复发性子宫内膜间质肉瘤（ESS） (7;17)(p15;q21) 染色体易位与这些肿瘤相关。两个都 基因编码含有锌指结构域的蛋白质，在 JAZF1 中， 两个这样的域的密码子序列与两个域的密码子序列非常相似 最近在转录因子 Sfplp 中发现了锌指 与控制细胞周期中 G2/M 检查点的机制有关 酿酒酵母。他建议表征肿瘤中的 JAZF1 和 2 基因 正常组织通过一系列研究，首先完成 正常编码氨基末端的核苷酸序列分析 序列，尚未找到。种类繁多的子宫和 将筛查非子宫肉瘤的融合转录本和突变 JAZF1 基因以确定包含异常的肿瘤范围 在这两个基因中，并回答了一些有关的悬而未决的问题 子宫间质瘤的分类和组织发生。此外， JAZF1/JAZF2融合诱导恶性转化的能力 使用培养细胞和转基因小鼠进行研究。基因表达 因 JAZF1/JAZF2 融合的存在而改变的情况将通过检查进行分析 培养细胞中的转录谱携带这两个基因的 cDNA 转染到细菌中。两者蛋白质产物之间的相互作用 将使用酵母双杂交系统探索基因和其他蛋白质。 将评估 JAZF1 和 2 的小鼠同源物的表型效应 在两个等位基因分别有缺陷的基因敲除动物中。最后，DNA结合 将寻找这两种蛋白质的位点，并且这些位点的序列将 依次用于鉴定受 JAZF1 和 2 转录调控的基因 正常细胞。