深入剖析神经母细胞瘤中的拷贝数变异

发布时间：2018-10-31 11:09

【摘要】：神经母细胞瘤是一种最常见的儿童颅外肿瘤,起源于交感神经系统的任意神经脊部位,一般在5岁以下的儿童中较常见,平均年龄差不多18个月,有着高达15%以上的儿童肿瘤死亡率,有时,在一些10岁左右的儿童中,也会有很少数患病。而目前神经母细胞瘤真正的致病分子机理尚不清楚,但是一些易感基因,或者一些染色体异常对神经母细胞瘤疾病的产生有着重要的作用。随着对基因组序列的不断研究,RNA-Seq测序技术、全基因组测序技术和Exome-Seq测序技术等技术的不断进步,我们在发现越来越多的SNPs对疾病的有影响的同时,也发现基于拷贝数变异对基因组序列的研究和疾病的研究占据着越来越显著的地位。通过阅读文献,我们知道拷贝数变异对神经神经母细胞瘤起了很重要的作用,而且大量的实验结果也证实了很多拷贝数变异位置对神经母细胞瘤的作用。在此,为了更好更全面的了解神经母细胞瘤中的拷贝数变异,我们对神经母细胞瘤中的变异,特别是拷贝数变异进行有效的分析和获取有效的结果。由于近些年来,第二代测序技术的发展和成熟,我们对498个神经母细胞瘤病人进行高通量数据测序,对所有的神经母细胞瘤病人都进行RNA-Seq高通量测序,同时对其中的30个病人正常和对照组进行Exome-Seq测序技术测序。通过对这些样本数据进行综合分析,检测数据中的拷贝数变异,通过对该数据的变异分析,结合相应的差异表达基因数据,我们不仅可以得到多个基因与神经母细胞瘤有可能相关,如：MYCN, NBAS, NAIP, DDX1等基因与神经母细胞瘤疾病有关,也发现了GTF2H2等新基因很可能与神经母细胞瘤相关；同时也发现了28个基因亚带可能与该疾病相关,其中包括基因亚带1q21.1、1q21.2等。特别是,发现了4q13.2、5q13.2、17p11.2和15q25.2这4个基因亚带非常有可能与致死神经母细胞瘤相关,在这些基因亚带中,包含了很多与神经母细胞瘤疾病相关的基因,以及一些对骨髓和神经元发育的有着重要作用的基因。不管这些基因,还是基因亚带的发现,对治疗神经母细胞瘤和个体治疗都有着很大的帮组。
[Abstract]:Neuroblastoma is one of the most common extracranial tumors in children. It originates from any part of the sympathetic nerve system and is more common in children under 5 years of age, with an average age of about 18 months. There are more than 15% of childhood cancer deaths, and sometimes a small number of children around the age of 10 suffer from the disease. At present, the mechanism of neuroblastoma is not clear, but some susceptible genes or some chromosomal abnormalities play an important role in the development of neuroblastoma. With the continuous research of genome sequence, RNA-Seq sequencing technology, whole genome sequencing technology and Exome-Seq sequencing technology, we find that more and more SNPs have influence on disease at the same time. It is also found that the study of genome sequence and disease based on copy number variation is becoming more and more important. By reading the literature, we know that copy number variation plays an important role in neuroblastoma, and a large number of experimental results also confirm the role of many copy number variation sites on neuroblastoma. In order to better understand the copy number variation in neuroblastoma, we analyze the variation in neuroblastoma, especially copy number variation, and obtain effective results. Due to the development and maturity of the second generation sequencing technology in recent years, 498 patients with neuroblastoma were sequenced with high-throughput data, and all patients with neuroblastoma were subjected to high-throughput RNA-Seq sequencing. At the same time, 30 of the patients were sequenced by Exome-Seq sequencing technique. Through the comprehensive analysis of these sample data, the copy number variation in the data is detected, and through the variation analysis of the data, combining with the corresponding differential expression gene data, We can not only find that many genes may be associated with neuroblastoma, such as: MYCN, NBAS, NAIP, DDX1 and other genes, but also find that new genes such as GTF2H2 may be associated with neuroblastoma. At the same time, 28 gene subbands were found to be related to the disease, including 1q21.1 / 1q21.2 and so on. In particular, four gene subbands, 4q13.2n5q13.2n17p11.2 and 15q25.2, are highly likely to be associated with lethal neuroblastoma, which contain many genes associated with neuroblastoma disease. And genes that play an important role in the development of bone marrow and neurons. Whether these genes or the discovery of gene subbands, there is a great deal of help in the treatment of neuroblastoma and individual therapy.
【学位授予单位】：华东师范大学
【学位级别】：硕士
【学位授予年份】：2014
【分类号】：R739.41

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