Molecular Profiling and Candidate Gene Analysis in Pediatric Gliomas

儿科胶质瘤的分子谱和候选基因分析

• 批准号: 7446270
• 负责人: JACLYN A BIEGEL
• 金额: $ 22.22万
• 依托单位: CHILDREN'S HOSP OF PHILADELPHIA
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-04-01 至 2010-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7446270
• 关键词: 7q34; Adult; Astrocytoma; Biological Markers; Brain Neoplasms; Candidate Disease Gene; Child; Childhood; Childhood Astrocytic Tumor; Childhood Brain Neoplasm; Childhood Glioma; Chromosomal Gain; Chromosome Band; Chromosome Banding; Chromosomes; Chromosomes, Human, Pair 7; Cytogenetics; DNA; Development; Diagnosis; Event; Fluorescent in Situ Hybridization; Freezing; Funding; Ganglioglioma; Gene Mutation; Genes; Genetic; Genomics; Genotype; Glioma; Goals; Histologic; Immunohistochemistry; Interphase; Juvenile Pilocytic Astrocytomas; Loss of Heterozygosity; Malignant Glioma; Malignant Neoplasms; Metaphase; Methods; Molecular Cytogenetics; Molecular Profiling; Mutation; Numbers; Operative Surgical Procedures; Patients; Polymerase Chain Reaction; Preparation; Primary Neoplasm; Public Health; RNA analysis; Recurrence; Research; Resistance; Resolution; Risk; Sequence Analysis; Series; Single Nucleotide Polymorphism; Solid Neoplasm; Specificity; Specimen; Standards of Weights and Measures; TP53 gene; Technology; Trisomy 7; base; comparative genomic hybridization; density; design; novel; outcome forecast; positional cloning; tumor

DESCRIPTION (provided by applicant): Pediatric low-grade gliomas constitute the most common group of solid tumors in children. Despite the utilization of a variety of cytogenetic and molecular approaches, the primary genetic events associated with the development of pediatric low-grade gliomas are largely unknown. Although the majority of children may be cured with surgery alone, tumors can recur. Often the recurrences are of a higher malignancy grade, and may be resistant to treatment. There are currently no histologic or biologic markers that can be used to identify which patients are at an increased risk for recurrence. With recent developments in array technology, we now have the opportunity to characterize the genomic alterations in pediatric gliomas at an extremely high level of resolution. We hypothesize that specific non-random chromosomal imbalances will be detected using these approaches. In this application, we propose three specific aims. In aim 1, we will analyze a series of pediatric astrocytomas and gangliogliomas using 550K single polymorphism nucleotide arrays from Ilumina. Chromosomal gains and losses, as well as regions of copy number neutral loss of heterozygosity will be identified. In aim 2, we will validate the array results and identify candidate genes using a combination of fluorescence in situ hybridization, DNA and RNA analysis and immunohistochemistry. In aim 3, specific markers and potential candidate genes will be analyzed in a series of low and high-grade gliomas from both children and adults to determine the specificity of the markers or genomic alterations for different groups of patients. The ultimate goal of this Research is to identify specific markers that can be used as an aid in the diagnosis, prognosis, and ultimate treatment of gliomas in children. PUBLIC HEALTH RELEVANCE: Pediatric gliomas are the most common types of solid tumors in children. We will use high-density single nucleotide polymorphism arrays to detect novel chromosomal changes in these tumors. Our studies will form the basis for ultimate identification of the genes that are responsible for the development or progression of gliomas, thus allowing for development of biologically based treatment strategies.

描述（由申请人提供）：小儿低级神经胶质瘤构成儿童最常见的实体瘤。尽管利用了多种细胞遗传学和分子方法，但与小儿低级神经胶质瘤发展有关的主要遗传事件在很大程度上尚不清楚。尽管大多数儿童可能仅通过手术治愈，但 肿瘤可以复发。通常，复发率具有更高的恶性级，并且可能对治疗有抵抗力。目前尚无组织学或生物学标志物可以用于确定哪些患者的复发风险增加。随着阵列技术的最新发展，我们现在有机会以极高的分辨率来表征小儿神经胶质瘤的基因组改变。我们假设使用这些方法检测到特定的非随机染色体失衡。在此应用程序中，我们提出了三个具体目标。在AIM 1中，我们将使用来自Ilumina的550K单一多态性核苷酸阵列分析一系列小儿星形胶质细胞瘤和神经节瘤。将确定染色体的收益和损失以及拷贝数中性损失的区域。在AIM 2中，我们将验证阵列结果并使用原位杂交，DNA和RNA分析和免疫组织化学的荧光组合鉴定候选基因。在AIM 3中，将在儿童和成人的一系列低级和高级神经胶质瘤中分析特定的标记和潜在候选基因，以确定 不同组患者的标记或基因组改变。这项研究的最终目的是确定可以用作儿童神经胶质瘤的诊断，预后和最终治疗的特定标记。 公共卫生相关性：小儿神经胶质瘤是儿童最常见的实体瘤类型。我们将使用高密度的单核苷酸多态性阵列来检测新型染色体 这些肿瘤的变化。我们的研究将构成最终鉴定负责神经胶质瘤发展或进展的基因的基础，从而允许发展基于生物学的治疗策略。