Mutational Profiling of A Long-term Surviving Stage Ⅲ Colore

发布时间：2022-01-10 20:09

　　结直肠癌（CRC）是最常见的胃肠道恶性肿瘤之一。在发达国家和发展中国家,结直肠癌均是男性和女性由于癌症致死的第二大最常见原因。在所有结直肠癌的报告病例中,Ⅲ期患者所占比例为三分之一。通常Ⅲ期患者的预后较差,30-50%病人在5年内会出现肿瘤复发和转移。本研究工作的重点是使用二代测序技术和生物信息学工具来分析一名长期存活的Ⅲ期结直肠癌患者的突变情况,并将所得到的基因组信息与The Cancer Genome Atlas（TCGA）数据库进行比较。本论文中,我们研究了一位40岁中国汉族女性患者的病例的基因组变异情况。该患者有结直肠癌相关的症状,包括腹部不适、里急后重和严重背痛,并于2008年10月被安徽医科大学第一附属医院接诊入院。其肿瘤大小为3cm×3cm,并已侵袭了浆膜层,肿瘤覆盖肠管的3/4。患者经检查后被诊断为Ⅲ期结直肠癌。该患者经过根治性手术和中药奥沙利铂和槐耳颗粒的辅助治疗后,预后良好,生存期超过8年。我们通过全基因组测序,分析了生殖系突变和体细胞突变,并获得了基因组改变的全部数据。我们在该患者中鉴定出194个生殖系突变。经过公共数据库过滤后,其中有20个生殖系突变基因与Can... 

【文章来源】：中国科学技术大学安徽省 211工程院校 985工程院校

【文章页数】：113 页

【学位级别】：博士

【文章目录】：
DEDICATION
ACKNOWLEDGEMENTS
ABSTRACT
摘要
LIST OF ABBREVIATIONS
CHAPTER 1 Introduction
    1.1 Risk factors of colorectal cancer
        Non-modifiable factors
            Age
            History of adenomatous polyps
            Family history of colorectal cancer
            Inherited genetic risk
        Modifiable factors
            Environmental risk factors
            Nutritional practices
            Physical activity and obesity
            Cigarette smoking
            Heavy alcohol consumption
    1.2 Colorectal cancer diagnosis and staging
    1.3 Tumor staging
    1.4 Colorectal cancer symptoms
    1.5 Management of colorectal cancer
        Surgery
        Chemotherapy for resectable metastatic colorectal cancer
        Chemotherapy for Unresectable Metastatic Colorectal cancer
        Combination chemotherapy with Traditional Chinese Medicine
    1.6 Next-Generation Sequencing Technology
        Second-generation sequencing platforms
    1.7 NGS applications in cancer research
        Whole Genome Sequencing
        Targeted DNA Sequencing
        Exome sequencing
        RNA Sequencing
    1.8 Dissertation outline
CHAPTER 2 Materials and Methods
    2.1 Study samples
    2.2 DNA extraction and library preparation
    2.3 Whole genome sequencing
    2.4 Bioinformatics analysis
        2.4.1 Mapping
        2.4.2 Marking of reads duplicates
        2.4.3 Local realignment and base quality score recalibration
        2.4.4 Germline variants detection
        2.4.5 Somatic variants detection
            2.4.5.1 Lancet
            2.4.5.2 Mutect
            2.4.5.3 SomaticIndelDetector
        2.4.6 Annotations
            2.4.6.1 ANNOVAR
            2.4.6.2 VEP
            2.4.6.3 The 1000 Genomes Project
            2.4.6.4 The Exome Aggregation Consortium
        2.4.7 Copy number alternation and structural variation analysis
        2.4.8 Evaluation of somatic mutational signature
    2.5 Mutation significance analysis
    2.6 Gene Ontology Enrichment analysis
    2.7 TCGA analysis
CHAPTER 3
    3.1 Tumor purity and coverage statistics
    3.2 Germline mutations
    3.3 Somatic mutations
    3.4 Mutational signatures in the patient
    3.5 Structural variation and copy number alternation analysis
    3.6 Gene Ontology enrichment
    3.7 TCGA results
    3.8 Discussion
CHAPTER 4
    4.1 Conclusions
    4.2 Future perspectives
References
Publications



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