MOLECULAR INVESTIGATION OF FAMILIAL WILMS TUMOR

描述：（改编自研究者摘要）一项修订后的应用程序，用于测试Wilms肿瘤的肿瘤发生是由肿瘤细胞中多个位点的种系或体细胞突变引起的假设。已知一个Wilms肿瘤基因：染色体11p上的转录因子WT1。PI建议在chr19q上精细定位遗传性肾母细胞瘤的第二个位点WT2，并确定负责基因。具体目标是：(1)确定并取样具有家族WT的其他家族；(2)确定与19q相关的子集（以及与WT相关的其他区域相关的任何家族）；(3)探索所有家族病例，无论是否与19q相关，对于涉及19q关键区域或涉及WT的其他区域的LOH；(4)利用减数分裂重组、杂合缺失和不平衡等方法，在该区域的物理图谱上确定19q WT2位点的位置；(5)筛选WT患者种系和体细胞突变区域的候选基因和ESTs

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