SECOND MALIGNANCY IN RETINOBLASTOMA--ROLE FOR IMPRINTING

视网膜母细胞瘤中的第二种恶性肿瘤——印记的作用

• 批准号: 3426606
• 负责人: catherine driscoll
• 金额: $ 3.86万
• 依托单位: WEILL MEDICAL COLL OF CORNELL UNIV
• 依托单位国家: 美国
• 财政年份: 1990
• 资助国家: 美国
• 起止时间: 1990-07-16 至 1992-07-15
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3426606
• 关键词: DNA; alleles; autoradiography; cancer complication; cancer risk; chemical cleavage; deoxyribonuclease I; electrophoresis; gene deletion mutation; gene expression; genetic promoter element; genetic transcription; heterozygote; human tissue; hypersensitivity; lymphocyte; methylation; molecular oncology; neoplasm /cancer genetics; nucleic acid probes; oncogenes; osteosarcoma; polymerase chain reaction; retinoblastoma

Retinoblastoma (Rb) is an embryonal tumor of early childhood occuring at a frequency of 1/23,000 live births. Approximately 40% of Rbs are due to a germinal mutation expressed as a dominant trait. This mutation also predisposes to the development of second nonocular malignancies notably sarcomas. It is unclear if all Rb patients have the same risk of developing second malignancies. Rb has served as a prototype for a model of tumorigenesis proposed by Knudsen. This model requires two successive event is germinal, while the second event may be chromosomal loss/duplication, deletion, point mutation or mitotic recombination resulting in functional loss of the normal allele. The recent observation tumor, and rhabdomyosarcoma, however, suggests that a phenomenon called genomic imprinting, may be involved in preferential inactivation of the paternal genome in these tumors. Genomic imprinting is an epigenetic process in which the expressivity/penetrance of a gene may be dependent upon the parental origin. We propose to study the role of imprinting, if any, in the development of second malignancies in hereditary Rb by, (1) determining if there are tissue specific differences in methylation of promotor in peripheral blood lymphocyte, retinoblastoma, and osteogenic sarcoma DNA samples, (2) analyze constitutional and tumor (1o and 2o) tissues for loss of heterozygosity, Rb gene deletions, Rb mRNA expression, and parental origin. (3) analyze our pedigrees (where possible) for parental origin of Rb gene in cases of nonocular malignancies.

视网膜母细胞瘤（Rb）是一种发生于儿童早期的胚胎性肿瘤， 1/23，000活产的频率。 大约40%的RBS是由于 表现为显性性状的基因突变。 这种突变也 易发生第二种非眼部恶性肿瘤， 肉瘤 目前尚不清楚是否所有Rb患者都有相同的风险， 发展成第二种恶性肿瘤 Rb已经作为一个模型的原型 肿瘤发生的理论。 该模型需要两个连续的 第一个事件是染色体，而第二个事件可能是染色体 缺失/重复、缺失、点突变或有丝分裂重组 导致正常等位基因的功能丧失。 最近提出的意见 肿瘤和横纹肌肉瘤，然而，表明一种称为 基因组印记，可能参与优先失活的 父亲的基因组 基因组印记是一种表观遗传 基因的表达性/表达率可能依赖于 关于父母的起源 我们建议研究印记的作用，如果 任何，在遗传性Rb的第二种恶性肿瘤的发展中，（1） 确定是否存在甲基化的组织特异性差异， 外周血淋巴细胞、视网膜母细胞瘤和成骨细胞 肉瘤DNA样品，（2）分析体质和肿瘤（1 o和2 o） 组织的杂合性缺失、Rb基因缺失、Rb mRNA表达， 和父母的血统 (3)分析我们的血统（如果可能）， 非眼部恶性肿瘤Rb基因的双亲来源