Title Page
Contents
ABSTRACT 7
I. Introduction 8
II. Materials and Methods 10
1. Study population and samples 10
2. Conventional study 10
3. Targeted gene sequencing 10
1) Gene panel 10
2) Predisposition syndrome to hematologic malignancies 11
3) Data analysis 12
4. Statistical analysis 12
III. Results 13
1. Patients 13
2. Germline sequence variants among 23 syndrome-associated genes 13
1) Pathogenic or likely pathogenic variants 13
3. Germline sequence variants in genes other than those associated with the 23 syndromes 14
4. Germline copy number variants 14
5. Somatic sequence variants 15
1) T-ALL 15
2) B-ALL 15
6. Somatic copy number variants 16
1) CDKN2A/B by NGS and FISH 16
2) T-ALL 16
3) B-ALL 17
7. Clinical effects of genetic alteration 17
1) Overall survival and relapse-free survival 17
2) Clinical impact of IKZF1 17
IV. DISCUSSION 18
V. References 24
논문요약 52
Table 1. Genes included in the hematologic cancer panel. 30
Table 2. Clinical characteristics of 93 ALL patients. 31
Table 3. Germline pathogenic or likely pathogenic variants identified in Korean ALL patients. 32
Table 4-1. Thirty germline pathogenic or likely pathogenic variants (excluding genes associated with 23 syndromes). 33
Table 4-2. Thirty germline pathogenic or likely pathogenic variants (excluding genes associated with 23 syndromes) 34
Table 5. Somatic sequence variants identified in Korean ALL patients. 36
Table 6. Somatic sequence variants by pathway. 40
Table 7. Somatic CNVs by pathway. 41
Table 8. Comparison of FISH and NGS results for CDKN2A/B deletion/duplication. 42
Table 9. IKZF1 alteration cases. 43
Figure 1. Workflow of the NGS data analysis. 44
Figure 2. CASP10 gene deletion detected by the NGS CNV analysis in a patient with B-ALL. 45
Figure 3. Somatic sequence variants in ALL patients. 46
Figure 4. Somatic sequence variants by cytogenetic group. 47
Figure 5. Somatic gene CNVs in ALL patients. 48
Figure 6. Somatic gene CNVs by cytogenetic group. 49
Figure 7. Clinical outcomes by cytogenetic group. 50
Figure 8. Clinical outcomes by IKZF1 alteration. 51