同源重组缺陷：基因组特征的产生方式。
Homologous recombination deficiency: how genomic signatures are generated.
机构信息
Dept. of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, NY, United States.
Dept. of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY, United States.
出版信息
Curr Opin Genet Dev. 2021 Feb;66:93-100. doi: 10.1016/j.gde.2021.01.002. Epub 2021 Jan 18.
Abstract
Cancer genomes harbor mutational and structural rearrangements that are jointly shaped by DNA damage and repair mechanisms. Accumulating evidence suggests that genetic alterations in DNA repair-defective tumors reflect the scars caused by the use of backup DNA repair mechanisms needed to maintain cellular viability. Detailed analysis of the patterns of mutations and structural rearrangements present in BRCA1/2-deficient tumors has allowed for the delineation of genomic signatures that reflect alternative repair with inactive homologous recombination (HR). Here we aim to summarize recent advances in the analysis of genomic signatures associated with HR-deficiency and examine recent studies that have shed light on the backup repair mechanisms responsible for genomic scarring in HR-deficient tumors.
摘要
癌症基因组中存在突变和结构重排，这些改变是由 DNA 损伤和修复机制共同塑造的。越来越多的证据表明，DNA 修复缺陷肿瘤中的遗传改变反映了维持细胞活力所需的备用 DNA 修复机制所造成的“疤痕”。对 BRCA1/2 缺陷肿瘤中存在的突变和结构重排模式的详细分析，使得能够描绘出反映无活性同源重组（HR）替代修复的基因组特征。在这里，我们旨在总结与 HR 缺陷相关的基因组特征分析的最新进展，并探讨最近的研究，这些研究揭示了 HR 缺陷肿瘤中导致基因组“疤痕”的备用修复机制。
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