MOLECULAR INVESTIGATION OF FAMILIAL WILMS TUMOR

产品说明：（改编自研究者摘要）修订后的应用程序，用于检验Wilms肿瘤的肿瘤发生是由肿瘤细胞中一个以上基因座的突变（生殖系或体细胞）引起的假设。一个Wilms肿瘤基因是已知的：染色体11 p上的转录因子WT 1。PI建议在chr 19 q上精细定位遗传性Wilms瘤的第二个基因座WT 2，并确定负责基因。具体目标是：（1）确定并采样具有家族性WT的额外家族;（2）鉴定显示与19 q连锁的子集（3）研究所有家族性病例，无论是否与19 q相关，是否存在涉及19 q关键区域或其他与WT相关区域的洛合性缺失;（4）使用减数分裂重组、杂合性丢失和不平衡方法在该区域的物理图谱上精确定位19 q WT 2基因座;和（5）筛选该区域中的候选基因和EST，用于WT患者的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