GENETICS OF PEDIATRIC RHABDOID TUMORS

横纹肌样瘤是一种快速致命的恶性肿瘤， 在生命的头两年。 肿瘤可能存在于各种 身体的位置，但最常见于大脑， 肾 据报道，一些患者同时患有原发性中央性 神经系统恶性肿瘤和原发性肾横纹肌样瘤， 提示肿瘤具有共同的分子病因学。 我们有 报告称，脑横纹肌样瘤，或横纹肌样瘤的变体， 称为非典型畸胎样肿瘤的肿瘤的特征在于： 单体性或22号染色体缺失。 细胞遗传学和 分子研究已经被用来定义一个关键区域， 22q11.2可能是横纹肌样瘤基因座。 我们 假设肿瘤纯合缺失或失活 该区域内的抑制基因负责发育 儿童中枢神经系统肾横纹肌样瘤的研究， 和肾外组织。 这个轨迹的最小临界区域 小于500 kb，并跨越免疫球蛋白之间的区域， 基因座和BCR基因。 我们建造了一个连续重叠的 一组Cosmetic和细菌人工染色体（BAC）， 跨越横纹肌样肿瘤的关键区域。 宇宙飞船和BAC将 用于分离横纹肌样瘤基因的候选cDNA， 大规模基因组序列分析与外显子分析相结合 诱捕方法 然后将对候选基因进行基因组分析， 匹配的m=正常和肿瘤组织中的改变和突变， 横纹肌样瘤患者。 我们将确定基因组 并分析其在正常组织和肿瘤组织中的表达 组织中 横纹肌样瘤基因的鉴定将是 有助于设计灵敏的诊断分析，以及 改善治疗方案。

Rhabdoid tumor is a rapidly fatal malignancy which generally presents in the first two years of life. The tumors may present in various locations of the body, but are most often seen in the brain and Kidney. Some patients have been reported with both a primary central nervous system malignancy and a primary renal rhabdoid tumor, suggesting that the tumors have a common molecular etiology. We have reported that rhabdoid tumor of the brain, or a variant of rhabdoid tumor referred to as a atypical teratoid tumor, is characterized by monosomy or deletion of chromosome 22. Combined cytogenetic and molecular studies have been used to define a critical region in 22q11.2 which we proposed contains a rhabdoid tumor locus. We hypothesize that homozygous deletion or inactivation of a tumor suppressor gene within this region is responsible for the development of pediatric rhabdoid tumors of the central nervous system kidney, and extra-renal tissues. The minimal critical region for this locus is less than 500 kb, and spans the region between the immunoglobulin loci and the BCR gene. We have constructed a contiguous overlapping set of cosmids and bacterial artificial chromosomes (BACs) which spans the rhabdoid tumor critical region. The cosmids and BACs will be used to isolate candidate cDNAs for the rhabdoid tumor gene by a combination of large scale genomic sequence analysis and exon trapping methods. Candidate genes will then be analyzed for genomic alterations and mutations in matched m=normal and tumor tissue from patients with rhabdoid tumors. We will determine the genomic structure of the gene, and analyze its expression in normal and tumor tissues. Identification of the rhabdoid tumor gene will be a major contribution towards the design of sensitive diagnostic assays, and improved treatment protocols.