Single Nucleotide Polymorphisms In Intraocular Lymphoma

眼内淋巴瘤的单核苷酸多态性

• 批准号: 6968559
• 负责人: ROBERT B. NUSSENBLATT
• 金额: --
• 依托单位: NATIONAL EYE INSTITUTE
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/6968559
• 关键词: eye neoplasms; gene frequency; genetic susceptibility; human tissue; immunogenetics; interleukin 10; interleukin 6; lymphoma; single nucleotide polymorphism

There is no known underlying genetic defect predisposing patients to develop primary intraocular lymphoma (PIOL). Discovery of genetic factors predisposing to the development of PIOL would be of benefit for early diagnosis, prognostic staging, and development of novel treatments for PIOL. Until recently, genetic approaches to investigate the etiology of cancer have relied upon methods utilizing linkage based on traditional Mendelian inheritance patterns. It is probable that many diseases are a consequence of multiple genetic factors, and are therefore less amenable to study using traditional methods of linkage analysis and positional cloning to isolate single genes. Single nucleotide polymorphisms (SNPs) are the most common sources of variation in the human genome. SNPs are single-base differences in the DNA sequence that can be observed among individuals in a population. A SNP is defined on the basis of a frequency of at least 1% prevalence in one or more populations. SNPs are present throughout the genome at an average frequency of 1/1000 base pairs. We propose to analyze the frequency of SNPs specifically within the coding frames of biologically plausible genes responsible for function of the innate immune system. The interleukins are a specific pathway of interest because previous research has demonstrated derangements in the ratios of interleukins 10 and 6 in the vitreous humor and spinal fluid of patients with PIOL, leading to the hypothesis that altered function or expression of these or other interleukins could permit the development of this rare malignancy. Samples continue to be collected, but as no results have yet been obtained. We hosted a workshop on this subject at the NIH recently and we plan to contact participants to gain specimens for this rare tumor.

没有已知的潜在遗传缺陷诱发患者发展原发性淋巴瘤（PIOL）。发现偶然发展的遗传因素的发现对于早期诊断，预后分期以及对PIOL的新型治疗方法的发展将是有益的。直到最近，研究癌症病因的遗传方法一直依赖于基于传统的孟德尔遗传模式的联系的方法。许多疾病很可能是多种遗传因素的结果，因此使用传统的链接分析和位置克隆来研究以分离单个基因的位置克隆的研究不足。单核苷酸多态性（SNP）是人基因组中最常见的变异来源。 SNP是DNA序列中可以观察到的DNA序列的单基差异。根据一个或多个人群中至少1％的患病率定义了SNP。 SNP在整个基因组中存在，平均频率为1/1000碱基对。我们建议在负责先天免疫系统功能的生物学上合理基因的编码框架内专门分析SNP的频率。白细胞介素是一种特定的感兴趣途径，因为先前的研究表明，白细胞介素10和6的玻璃体幽默和脊髓液在患有PIOL患者的玻璃体中的危险，导致假设改变了这些或其他杂星的功能或表达可能会允许这种罕见的恶性肿瘤的发展。样品继续被收集，但由于尚未获得结果。我们最近在NIH举办了有关此主题的研讨会，我们计划与参与者联系，以获取这种罕见肿瘤的标本。