臺灣博碩士論文加值系統

TP53基因在許多癌症的腫瘤抑制和進展中扮演著重要的作用，迄今為止，TP53的改變與許多癌症有關連，儘管與其他類型的癌症相比，診斷患者中TP53改變的發生率較低，但其在小兒科中復發的急性淋巴細胞白血病的改變似乎更為高。然而，結果仍然缺乏充分的驗證，並沒有全面探索所有的改變，因此，在本研究中，藉由核酸定序 (Sanger sequencing) 和多重連接依賴性探針擴增技術（MLPA）分別檢測到TP53體細胞基因體變異，其中包括了單核苷酸變異（SNV）、小片段剃除、插入或移碼。最後，還評估了上述鑑定的TP53基因體細胞基因組變異在小兒復發的急性淋巴細胞白血病預後之影響。這項研究的結果可能有機會為小兒復發的急性淋巴細胞白血病提供預測分子標記，並為精準醫學中提供更精確的分子治療。

TP53 gene plays an important role in tumor suppression and progression in many cancers. Up to date, TP53 alterations were associated with many cancers. Although the incidence of TP53 alterations was low in the diagnostic patients in comparison with other types of cancer, its alterations seemed enriched in pediatric of relapsed acute lymphocytic leukemia (ALL). However, the results are still lack of sufficient validation and not all alterations were explored comprehensively. Hence, in this study, somatic genomic variations of TP53 comprising single nucleotide variations (SNVs), small fragment deletions, insertion or frame-shift were detected through Sanger sequencing or multiplex ligation-dependent probe amplification (MLPA), respectively. Finally, the impact of the prognosis of above identified somatic genomic variations were also evaluated. Findings of this study may have chance to provide predictive molecular markers for childhood ALL and molecular guidance of patient managements in precision medicine.

口試委員審定書………………………………………………………………………i
致謝…………………………………………………………………………………….ii
中文摘要……………………………………………………………………………….iii
ABSTRACT…………………………………………………………………………….iv
LIST OF FIGURES……………………………………………………………………...5
LIST OF TABLES…………………………………………………………………….....6
CHAPTER 1……………………………………………………………………………..7
1.1 Introduction………………………………………………………………………….7
1.2 Material and Methods………………………………………………………………11
1.2.1 Patients and data collection………………………………………………………11
1.2.2 DNA extractions………………………………………………………………….11
1.2.3 Sanger sequencing of detail information…………………………………………11
1.2.4 TP53 deletions detected by MLPA……………………………………………….12
1.2.5 Statistical analysis………………………………………………………………...13
1.3 Results……………………………………………………………………………...14
1.3.1 Frequency and type of TP53 alterations in relapsed childhood ALL…………….14
1.3.2 Correlations of TP53 mutations with TP53 deletions……………………………16
1.3.3 Analysis of TP53 alterations in matched diagnosis and relapse patients………...16
1.3.4 Analysis of TP53 alterations of clinical characteristic and survival rate………...17
1.3.5 TP53 alterations is in association with time of relapse in this study……………..19
1.4 Discussions…………………………………………………………………………21
REFERENCES…………………………………………………………………………43

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