BACKTRACKING TRANSLOCATIONS IN CHILDHOOD LEUKEMIA

描述(改编自研究人员摘要)：儿童病因学 白血病目前正在#年进行大规模流行病学研究。 美国和英国。调查人员建议检查时间和病因 儿童急性淋巴细胞性白血病最常见的遗传异常 急性髓系白血病(ALL和AML)的分子生物学和分子生物学研究 患者诊断和存档材料中的生物信息学工具和资源。 研究人员此前已经证明，最常见的易位是 儿童白血病，t(12；21)(或TEL-AML1基因融合)可在出生前发生 在少数后来患上儿童白血病的人中。这些 研究将扩大并扩大到#年的独立人口。 加利福尼亚。约150例有特殊像差的患者，包括t(12；21)， T(1；19)、t(8；21)和NRAS突变将通过筛查 新生儿跟部跟部穿刺点的异常 出生。这些异常将首先在基因组DNA水平上进行表征， 然后将其作为克隆型标记用于敏感筛选试验。 格思里斑点。 除了作为白血病细胞克隆的标记外，易位 融合序列提供了对形成融合的过程的洞察。 TEL-AML1融合连接倾向于分组为“微簇”，或不同的 较大的内含子断点簇区内的区域。这个 微聚集性与嵌合致癌基因的结构无关 蛋白质，这对所有的患者都是一样的。中断点的微聚类 某些区域提示固有DNA序列或染色质的特征 结构在易位的形成过程中起着关键作用。这些 特征将通过基于统计学的DNA序列识别工具进行探测 同时进行协调的实验室分析以确定序列基序。一个 该项目的最终目标是开发灵敏地追踪白血病的方法 在接受治疗的患者中进行克隆，以衡量治疗的成功。在……里面 综上所述，本项目旨在阐明基因的时间和结构 导致儿童白血病的事件。

DESCRIPTION (Adapted from investigator's abstract): The etiology of childhood leukemia is currently being examined under large-scale epidemiology studies in the US and UK. The investigator proposes to examine the timing and etiology of the most frequent genetic aberrations in childhood acute lymphoblastic and myeloblastic leukemia (ALL and AML) by using molecular biology and bioinformatic tools and resources in patient diagnostic and archived materials. The investigator has previously shown that the most common translocation in childhood leukemia, t(12;21) (or TEL-AML1 gene fusion) can occur before birth in a small number of individuals who later developed childhood leukemia. These studies will be expanded and extended to an independent population in California. About 150 patients with specific aberrations, including t(12;21), t(1;19), t(8;21), and NRAS mutations, will be "backtracked" by screening for the aberration in the neonatal heel-prick Guthrie spots that were taken at birth. The aberrations will first be characterized at the genomic DNA level, and then will be used as clonotypic markers in sensitive screening assays of Guthrie spots. In addition to this use as markers of leukemia cell clones, translocation fusion sequences provide insight into the processes that formed the fusion. TEL-AML1 fusion junctions tend to group into "micro-clusters," or distinct regions within the larger intronic breakpoint cluster regions. The micro-clustering is independent of the structure of the chimeric oncogenic protein, which is the same for all patients. Micro-clustering of breakpoints in certain areas suggests that features of the intrinsic DNA sequence or chromatin structure are critical in the process of formation of the translocation. These features will be probed by statistically based DNA sequence recognition tools along with a coordinated laboratory analysis to identify sequence motifs. A final goal of the project is to develop methods to sensitively track leukemia clones in treated patients in order to gauge the success of therapy. In summary, this project aims to elucidate the timing and structure of the genetic events that lead to childhood leukemia.