CANCER AND MORTALITY IN NEUROFIBROMATOSIS BY GENOTYPE

按基因型划分的神经纤维瘤病的癌症和死亡率

• 批准号: 7378097
• 负责人: John J. Mulvihill
• 金额: $ 0.28万
• 依托单位: UNIVERSITY OF OKLAHOMA HLTH SCIENCES CTR
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-03-01 至 2007-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7378097
• 关键词: CANCER; MORTALITY; NEUROFIBROMATOSIS; GENOTYPE

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The objective of this work is to assess the NF1 gene in individuals and their family members with neurofibromatosis (NF1) or suspected of having NF1. Assessing the mutations in NF1 genes is part of a larger project on the study of cancer and mortality in NF1 by genotype. Each patient will have a clinical evaluation at Children's Hospital of Oklahoma or elsewhere. During the visit the patients will receive counseling about NF1 and the risk and benefits of gene testing. This study will help us correlate specific mutations in the NF1 gene with specific phenotypes. The results may help the health care providers determine the risks of developing certain clinical features of NF1, which can lead to improved education and counseling concerning psychosocial factors, prognostic and other concerns of NF1 patients. A genotype-phenotype correlation could also help to introduce new therapies and interventions, and the effectiveness of genetic screening in predicting the disease and the outcome in the children of people with NF1. Improvements of a gene test for NF1 may be useful for ruling in or out a suspected diagnosis of NF1. We hypothesize that no mutation within the NF1 gene is associated with a specific endpoint, such as early death, a specific cancer, or any other medical event and that such events, in fact, show no significant clustering within families. The expected result is that at least one mutation, region of mutation, or class of mutation will appear to be associated with a certain endpoint, such as those families with NF1 that have an apparent excess of cancer. The work of the NIH grant parent that partly supports this gene assay has three specific aims. Specific Aim 1 - To determine the specific mutation within the NF1 gene in individuals and their family members. Specific Aim 2 - To explore possible NF1 mutation-specific associations with certain phenotypes. Specific Aim 3 - To assay the clinical validity of NF1 gene testing. During the clinical evaluation of study volunteers, we will usually construct a family tree, obtain medical history, and conduct targeted physical examination for diagnostic criteria of NF1. With the patient's (or parents') consent, we will request a blood sample for testing for NF1 mutations by a protein truncation assay, single-stranded conformation polymorphism gels, automatic fluorescent sequencing, RT-PCR, or other methods. The incidence of specific phenotypes will be compared by NF1 genotype. Buccal swabs may be an alternative source of DNA.

这个子项目是利用由NIH/NCRR资助的中心拨款提供的资源的许多研究子项目之一。子项目和调查员(PI)可能从另一个NIH来源获得了主要资金，因此可能会出现在其他CRISE条目中。列出的机构是针对中心的，而不一定是针对调查员的机构。这项工作的目的是评估患有神经纤维瘤病(NF1)或怀疑患有NF1的个人及其家庭成员的NF1基因。评估NF1基因的突变是一个更大的项目的一部分，该项目通过基因分型来研究NF1的癌症和死亡率。每个患者都将在俄克拉荷马州儿童医院或其他地方进行临床评估。在访问期间，患者将接受关于NF1以及基因测试的风险和好处的咨询。这项研究将帮助我们将NF1基因的特定突变与特定的表型联系起来。这一结果可能有助于卫生保健提供者确定发生NF1某些临床特征的风险，这可以导致改善关于NF1患者的心理社会因素、预后和其他问题的教育和咨询。基因-表型相关性也有助于引入新的治疗方法和干预措施，以及基因筛查在预测NF1患者子女疾病和结局方面的有效性。NF1基因检测的改进可能有助于排除或排除NF1的可疑诊断。我们假设，NF1基因内没有突变与特定的终点相关，例如过早死亡、特定的癌症或任何其他医学事件，事实上，这些事件在家庭中没有明显的聚集。预期的结果是，至少有一个突变、突变区域或突变类别似乎与某个终点有关，例如那些患有明显癌症过剩的NF1家族。部分支持这种基因分析的NIH赠款父母的工作有三个具体目标。具体目标1--确定NF1基因在个体及其家庭成员中的特定突变。具体目标2-探索NF1突变与某些表型的可能特异性关联。具体目的3：检测NF1基因检测的临床效度。在研究志愿者的临床评估中，我们通常会构建家系树，获取病史，并对NF1的诊断标准进行有针对性的体检。在征得患者(或父母)的同意后，我们将要求采集血液样本，通过蛋白质截断分析、单链构象多态凝胶、自动荧光测序、RT-PCR或其他方法检测NF1突变。特定表型的发生率将通过NF1基因型进行比较。口腔拭子可能是DNA的另一种来源。