肿瘤遗传异质性杨壹羚.pdf

HEREDITAS (Beijing) 2013 1 , 35(1): 1―9 ISSN 0253-9772 综 述 DOI: 10.3724/SP.J.1005.2013.00001 肿瘤遗传异质性 1 祐 2 3 杨壹羚 , 褚嘉 , 王明荣 1. , , , 300060; 2. , 650118; 3. , 100021 尽管大多数自发性肿瘤源于单细胞, 但人们逐渐认识到个体肿瘤的内部存在异质性, 这种差异涉及分化 程度、细胞增殖率、侵袭和转移能力及治疗反应等众多方面。分子生物学研究也证实肿瘤演进过程中不断产生 新的突变, 为肿瘤内部存在异质性增加了更有力的佐证。文章综述了关于肿瘤遗传异质性研究的主要进展。鉴 于遗传异质性分析可为揭示肿瘤细胞的产生、扩散、转移的时间段提供重要信息, 文章以瘤内异质性为主线, 列 举了遗传异质性存在的实验依据; 阐述了遗传多样性在人类个体肿瘤发展进化史中的研究价值; 介绍了遗传异 质性产生的两种模式, 包括肿瘤干细胞模型和克隆进化模型; 总结了遗传异质性在肿瘤转移、治疗中的重要临 床意义。文章最后展示了常用的遗传异质性的研究方法, 包括特定基因的分析方法和基于基因组水平的方法, 并对各自的优缺点进行了分析。 肿瘤; 遗传; 异质性 Tumor genetic heterogeneity 1 2 3 YANG Yi-Ling , CHU Jia-You , WANG Ming-Rong 1. Department of Breast Cancer Pathology and Research Laboratory, Key Laboratory of Breast Cancer Prevention and Therapy (Ministry of Education), Tianjin Medical University Cancer Institute Hospital, Tianjin 300060, China; 2. Institute of Medical Biology , Peking Union Medical College and Chinese Academy of Medical Sciences, Kunming 650118, China; 3. Cancer Institute (Hospital), Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing 100021, China Abstract: Although the majority of spontaneous tumors derive from a single cell, people have come to realize in- tra-tumor heterogeneity of individual tumors. Human cancers frequently display substantial difference in phenotypic fea- tures, such as the degree of differentiation, cell proliferation rate, invasion and metastatic po