Molecular Cloning of the Wilms tumor Gene from 7p15-21
7p15-21 肾母细胞瘤基因的分子克隆
基本信息
- 批准号:6785508
- 负责人:
- 金额:$ 18.92万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2003
- 资助国家:美国
- 起止时间:2003-08-01 至 2006-07-31
- 项目状态:已结题
- 来源:
- 关键词:Wilms&apos tumorbiotechnologydisease /disorder etiologygene deletion mutationgene expressionhigh performance liquid chromatographyhuman genetic material taghuman tissueloss of heterozygositymolecular cloningneoplasm /cancer geneticsnucleic acid denaturationpolymerase chain reactionserial analysis of gene expressiontumor suppressor genes
项目摘要
DESCRIPTION (provided by applicant): Wilms tumor is pediatric lesion of the kidney and is one of the most common solid malignancies of the childhood. Disease can occur in one or both kidneys, approximately 8% of cases being bilateral. The suggestion of a genetic component in the etiology of the tumor has come from several observations. Firstly, bilateral disease is associated with an early age of onset. Secondly, there is a high incidence of bilateral tumors in cases with a family history of Wilms tumor and in patients with associated congenital anomalies. Histological features indicate that the tumor occurs as a result of aberrant embryological development of the kidney. The kidney is therefore a model for studying the association between processes involved in tissue development and predisposition to malignancy. Although a gene for Wilms tumor (WT1) has been cloned, less than 10% of cases could be explained by mutations and/or alterations of this gene. Several other loci have been implicated in the etiology of Wilms tumors, including the 7p15-21 locus which was shown to be involved in 15-25% of Wilms tumors cases, strongly suggesting that a tumor suppressor gene for this disease must lie within this region. Since homozygous deletions are hallmarks of tumor suppressor genes, a homozygous deletion has been described in a Wilms tumor within the 7p15-21 locus and we have now characterized the extent of this deletion as a first step towards the identification of the Wilms tumor suppressor gene using a very powerful mutation analysis technology (DHPLC) and a large cohort of Wilms tumors, including those tumors that we have identified to show loss of heterozygosity at the 7p15-21 locus. By studying the expression pattern of this gene we will be able to identify the population of stem cells which give rise to these tumors. Understanding the nature of the genetic events which allow these cells to escape their normal growth regulation may also provide an opportunity for therapeutic intervention.
描述(由申请人提供):肾母细胞瘤是儿童肾脏病变,是儿童最常见的实体恶性肿瘤之一。疾病可以发生在一个或两个肾脏,大约8%的病例是双侧的。从几个观察结果中可以看出,肿瘤的病因学中有遗传成分。首先,双侧疾病与早期发病有关。其次,在有肾母细胞瘤家族史的病例和伴有相关先天性异常的患者中,双侧肿瘤的发病率很高。组织学特征表明,肿瘤发生的结果,异常胚胎发育的肾脏。因此,肾脏是研究组织发育过程与恶性肿瘤易感性之间关系的模型。虽然已经克隆了肾母细胞瘤(WT 1)的基因,但只有不到10%的病例可以通过该基因的突变和/或改变来解释。其他几个基因座也与肾母细胞瘤的病因有关,包括7 p15 -21基因座,该基因座被证明与15-25%的肾母细胞瘤病例有关,强烈表明这种疾病的肿瘤抑制基因必须位于该区域内。由于纯合缺失是肿瘤抑制基因的标志,因此在肾母细胞瘤中描述了7 p15 -21基因座内的纯合缺失,并且我们现在已经表征了这种缺失的程度,作为使用非常强大的突变分析技术(DHPLC)和大的肾母细胞瘤队列鉴定肾母细胞瘤肿瘤抑制基因的第一步,包括我们已经鉴定为在7 p15 -21位点显示杂合性丢失的那些肿瘤。通过研究该基因的表达模式,我们将能够识别引起这些肿瘤的干细胞群体。了解使这些细胞逃避正常生长调节的遗传事件的性质也可能为治疗干预提供机会。
项目成果
期刊论文数量(1)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
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KHALID SOSSEY-ALAOUI其他文献
KHALID SOSSEY-ALAOUI的其他文献
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