APOBEC Enzymes: Mutagenic Fuel for Cancer Evolution and Heterogeneity.
APOBEC Enzymes: Mutagenic Fuel for Cancer Evolution and Heterogeneity.
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DOI：
10.1158/2159-8290.cd-15-0344
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发表时间：
2015-07
期刊：
影响因子：
28.2
通讯作者：
Harris RS
中科院分区：
文献类型：
--
作者：
Swanton C;McGranahan N;Starrett GJ;Harris RS
深度测序技术揭示了癌症演变的复杂性，揭示了促进肿瘤适应、免疫逃逸和治疗抗性的突变过程。了解驱动癌症多样性的机制是制定减轻肿瘤演变和适应策略的关键一步。一种促进肿瘤多样性和亚克隆进化的新兴机制是由APOBEC3B和至少一种其他APOBEC家族成员催化的基因组DNA胞嘧啶脱氨基作用。APOBEC3酶的失调导致表现为多样性和异质性肿瘤亚克隆的一般突变体表型。在这里，我们总结了APOBEC DNA脱氨酶家族在癌症中的知识，以及它们作为肿瘤内异质性驱动力和限制肿瘤适应性的治疗靶点的作用。
Deep sequencing technologies are revealing the complexities of cancer evolution, casting light on mutational processes fuelling tumor adaptation, immune escape, and treatment resistance. Understanding mechanisms driving cancer diversity is a critical step toward developing strategies to attenuate tumor evolution and adaptation. One emerging mechanism fuelling tumor diversity and subclonal evolution is genomic DNA cytosine deamination catalyzed by APOBEC3B and at least one other APOBEC family member. Deregulation of APOBEC3 enzymes causes a general mutator phenotype that manifests as diverse and heterogeneous tumor subclones. Here we summarise knowledge of the APOBEC DNA deaminase family in cancer, and their role as driving forces for intratumor heterogeneity and a therapeutic target to limit tumor adaptation.