Diagnosis and Regulation of HER2 in Human Breast Cancer : 인간 유방암에서 HER2의 진단과 조절

목차 (Table of Contents)

• Ⅰ. Introduction 3
• 1.1 HER2 Diagnosis in breast cancer . 3
• HER2 oncogene 3
• Current HER2 testing 3
• Digital PCR-based HER2 evaluation 5
• 1.2 Transient oncogene amplification by histone methylation . 7
• Oncogene amplification on ecDNA 7
• Transient regulation of oncogene amplification by histone methylation 8
• HER2 amplification on ecDNA 9
• 1.3 Purpose of this study . 10
• Ⅱ. Materials and methods 14
• Ⅲ. Results . 26
• 3-1 Development of new HER2 diagnostic method using drPCR 26
• 3-1-1 Primer-probe sets design and optimization for analysis of HER2 copy
• number alteration using drPCR 26
• 3-1-2 Evaluation of HER2 status in breast cancer cell lines using drPCR 28
• 3-1-3 Establishment of drPCR-based assessment of HER2 status in FFPE
• tumor tissues from breast cancer patients 29
• 3-1-4 Validation of high accuracy of drPCR and identification of IHC false
• positives upon HER2 IHC re-evaluation. 31
• 3-1-5 Alternative CEP17 reference controls to precisely measure HER2 copy
• number status in CEP17 abnormalities 32
• 3-1-6 Identification of a point mutation in CEP17 region in breast cancer . 34
• 3-1-7 Proposed HER2 testing algorithm using drPCR . 35
• 3-2 Regulatory mechanism of HER2 in breast cancer . 36
• 3-2-1 SMYD3 histone methyltransferase upregulates HER2 expression . 36
• 3-2-2 SMYD3 epigenetically regulates HER2 in collaboration with ER . 38
• 3-2-3 SMYD3 induces HER2 copy number gain on ecDNA in breast cancer . 39
• Ⅳ. Discussion 67
• Ⅴ. References . 75
• Ⅵ. Abstract in Korean 94