THE JAZF1 AND 2 GENES IN UTERINE SARCOMAS

描述：(改编自调查人员的摘要)斯克拉尔博士 发现了两个以前未知的基因，称为JAZF1和2，它们被融合在 复发的低级别子宫内膜间质肉瘤(ESSS) (7；17)(p15；q21)染色体易位与这些肿瘤相关。两者都有 基因编码含有锌指结构域的蛋白质，而在JAZF1中， 两个这样的结构域的密码子序列与两个结构域的序列非常相似 在转录因子Sfplp中发现的锌指，最近被 参与调控细胞周期中G2/M检查点的机制 酿酒酵母。他建议对肿瘤中的JAZF1和2基因进行表征，并 通过一系列研究，从完成 正常编码蛋白氨基末端的核苷酸序列分析 序列，这些序列尚未被定位。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 用于确定包含异常的肿瘤的范围 并回答了一些悬而未决的问题 子宫间质瘤的分类和组织起源。此外， JAZF1/JAZF2融合蛋白诱导恶性转化的能力 使用培养细胞和转基因小鼠进行了研究。基因表达 由于JAZF1/JAZF2融合的存在而改变的将通过检查 培养细胞的转录图谱携带这两个基因的cdna。 被转入细菌中。两者的蛋白质产物之间的相互作用 基因和其他蛋白质将使用酵母双杂交系统进行探索。 将评估JAZF1和2的小鼠同系物的表型效应 在两个等位基因分别缺陷的基因敲除动物中。最后，DNA绑定 将寻找这两个蛋白质的位点，并将这些位点的序列 进而用于鉴定受JAZF1和2转录调控的基因 正常细胞。

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.