BIOLOGICAL PROGNOSTIC FACTORS IN WILMS TUMOR

描述（申请人的描述）：儿童的存活率 肾母细胞瘤有了显著改善。 预计的五年生存率 0-14岁儿童肾母细胞瘤的发病率为91.7%， 与同期比较， 1974-1976. 过去的治疗是基于肿瘤的范围（阶段）， 组织学 这些因素无法准确地确定15%的 尽管接受了现代治疗但病情复发的病人 我们建议评估几个 新的生物标志物，以确定它们是否可用于治疗前 将Wilms肿瘤患者分层为低水平， 复发的风险很高 我们将评估的因素是：1）损失 22 q和7 p杂合性; 2）GPC 3基因座突变; 3）端粒酶 肿瘤组织中的活性; 4）异常的WT 1 mRNA剪接;和5）WT 1 mRNA的缺失。 5 q杂合性 我们将研究这些潜在的标志物， 病例队列设计。 如果这些因素中的一个或多个被证明可以预测 复发，与分期和组织学无关，因素将是 使用累积的患者人群进行验证性分析 下一个国家威尔姆斯肿瘤研究小组治疗试验

DESCRIPTION (Applicant's Description): The survival rate for children with Wilms tumor has improved dramatically. The projected five-year survival rate for children 0-14 years of age with Wilms tumor is 91.7 percent, a statistically significant improvement when compared to that for the period 1974-1976. Treatment in the past was based on tumor extent (stage) and histology. These factors fail to accurately identify the 15 percent of patients who relapse despite modern therapy. We propose to evaluate several new biological markers to determine if they can be utilized for pre-therapy stratification of patients with Wilms tumor into those with a low, and those with a high risk of relapse. The factors we will evaluate are: 1) Loss of heterozygosity at 22q and 7p; 2) Mutation at the GPC3 locus; 3) Telomerase activity in tumor tissue; 4) Aberrant WT1 mRNA splicing; and 5) Loss of heterozygosity at 5q. We will study these potential markers using a case-cohort design. If one or more of these factors is shown to predict relapse, independent of stage and histology, that factor(s) will be investigated in a confirmatory analysis using the patient population accrued to the next National Wilms Tumor Study Group therapeutic trial.