MOLECULAR INVESTIGATION OF FAMILIAL WILMS TUMOR

描述：(改编自研究人员的摘要)一种修订的应用程序，用于测试Wilms肿瘤的肿瘤发生是由肿瘤细胞中多个位置的突变(种系或体细胞突变)导致的假设。已知一种Wilms肿瘤基因：位于染色体11p上的转录因子WT1。PI建议将遗传性肾母细胞瘤的第二个基因座WT2精细定位在chr19q上，并确定相关基因。具体目标是：(1)确定和采样更多具有家族性WTT的家系；(2)确定与19q连锁的子集(以及与WTT相关的其他区域的任何连锁的家系)；(3)探索所有家族性病例，无论是否与19q连锁，涉及19q上的关键区域或与WTT相关的其他区域；(4)利用减数分裂重组、杂合性丧失和不平衡方法，精炼19q WT2基因座在该区域物理地图上的位置；以及(5)在WTT患者中筛选该区域的候选基因和EST以寻找生殖系和体细胞突变。

DESCRIPTION: (Adapted from investigator's abstract) A revised application to test the hypothesis that tumorigenesis in Wilms tumor results from mutations, either germline or somatic, at more than one locus in the tumor cell. One Wilms tumor gene is known: the transcription factor WT1 on chromosome 11p. The PI proposes to fine map a second locus, WT2, for hereditary Wilms tumor on chr19q and identify the responsible gene. Specific Aims are: (1) Ascertain and sample additional families with familial WT; (2) identify the subset that show linkage to 19q (as well as any families linked to other regions implicated in WT); (3) explore all familial cases, whether linked to 19q or not, for LOH involving the critical region on 19q or other regions implicated in WT; (4) refine the position of the 19q WT2 locus on a physical map of the region using meiotic recombination, loss of heterozygosity, and disequilibrium approaches; and (5) screen candidate genes and ESTs in the region for germline and somatic mutations in WT patients