Title Page
ABSTRACT
국문 초록
Contents
CHAPTER 1. INTRODUCTION 14
CHAPTER 2. MATERIALS AND METHOD 16
2.1. Patient Samples 16
2.2. Materials 16
2.3. Genomic DNA and RNA isolation and measurement (quantity & quality) 17
2.4. Nucleic acid amplification and Library preparation 17
2.5. Next generation sequencing 18
2.6. NGS data analysis; Oncomine comprehensive assay 18
2.7. Statistical analysis 20
CHAPTER 3. RESULT 21
3.1. Patient characteristics 21
3.2. Genomic prevalence of somatic variants 22
3.3. Associations of the mutational status between frequently mutated genes 26
3.4. Genomic prevalence of copy number variations 28
3.5. Associations of CNVs status between altered genes 30
3.6. Genomic prevalence of gene fusions and intragenic deletions 32
3.7. Identification of actionable target genes for relevant therapy and clinical trials. 33
CHAPTER 4. DISCUSSION 40
REFERENCES 49
Table 1. Clinical characteristics of 147 patients with glioma 21
Table 2. Pathologic diagnosis of 147 patients with glioma 22
Table 3. Number of mutations (SNVs, InDels) detected for each pathological diagnosis of gliomas 23
Table 4. Distributions of representative genomic fusions and intragenic deletion in the different pathologic glioma 33
Table 5-1A. Targeted therapy of mutations (SNVs and InDels) 34
Table 5-1B. Clinical trials of mutations (SNVs and InDels) 34
Table 5-2. Clinical trials of CNVs (gene amplification) 36
Table 5-3. Clinical trials of fusions and intragenic deletion 38
Figure 1. A) Frequency of highly mutated 12 genes in 147 patients with glioma. The mutation frequency of highly mutated 9 genes in each pathological diagnosis of... 24
Figure 2. A) A combined plot of 64 genes correlated with each other. It shows the combination of 64 genes whose mutations are correlated with each other out of a... 26
Figure 2. B) Correlation heat map between 36 genes with significant correlation for each gene detected by more than one in a total of 68 genes (p-values〈0.05). 27
Figure 3. The distribution of copy number (CN) values in 25 genes, ranging from 6 up to 180. 29
Figure 4. A) A combined plot of 25 genes correlated with each other. This shows that the combination of CNVs in a total of 25 genes detected correlates with each... 30
Figure 4. B) Correlation heat map between 25 genes with significant correlation for each gene (p-values〈0.05). 31