Kasumi leukemia cell lines: characterization of tumor genomes with ethnic origin and scales of genomic alterations
Kasumi leukemia cell lines: characterization of tumor genomes with ethnic origin and scales of genomic alterations
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DOI：
10.1007/s13577-020-00347-5
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发表时间：
2020-03-16
期刊：
影响因子：
4.3
通讯作者：
Kawamura, Machiko
中科院分区：
文献类型：
--
作者：
Kasai, Fumio;Asou, Hiroya;Kawamura, Machiko
Kasumi-1在具有t（8;21）易位的实验模型中发挥了重要作用，该模型是白血病细胞系的代表性实例。然而，以前使用Kasumi-1的研究显示基因组图谱存在差异。白血病细胞系的广泛使用限于充分表征的细胞系。使用额外的细胞系将研究扩展到各种类型的白血病，并进一步探索白血病的发病机制，这可以通过用准确的数据揭示每个细胞系的基本特征来实现。在这项研究中，10个Kasumi细胞系在日本建立，其中包括五个以前是未知的，已通过SNP微阵列和靶向测序的特点。SNP基因分型表明，10个Kasumi细胞系中有4个的遗传祖先未被归类为日本人，但涵盖了几个不同的东亚种族，这表明日本患者的遗传多样性。TP 53突变在具有复杂阵列谱的两个细胞系中检测到，表明染色体不稳定性（CIN）。新引入了在染色体水平上对肿瘤基因组的定量评估，以揭示每种细胞系的总DNA大小和基因组改变规模（SGA）。Kasumi-1和Kasumi-6在复发期的肿瘤细胞中显示出高水平的SGA，这意味着SGA的水平可以反映肿瘤的进展，并可以作为CIN的指标。我们的研究结果扩展了白血病细胞资源，增加了5个细胞系，并为10个Kasumi细胞系提供了具有种族身份的参考基因组数据。
Kasumi-1 has played an important role in an experimental model with t(8;21) translocation, which is a representative example of leukemia cell lines. However, previous studies using Kasumi-1 show discrepancies in the genome profile. The wide use of leukemia cell lines is limited to lines that are well-characterized. The use of additional cell lines extends research to various types of leukemia, and to further explore leukemia pathogenesis, which can be achieved by uncovering the fundamental features of each cell line with accurate data. In this study, ten Kasumi cell lines established in Japan, including five that were previously unknown, have been characterized by SNP microarray and targeted sequencing. SNP genotyping suggested that the genetic ancestry in four of the ten Kasumi cell lines was not classified as Japanese but covered several different east-Asian ethnicities, suggesting that patients in Japan are genetically diverse. TP53 mutations were detected in two cell lines with complex array profiles, indicating chromosomal instability (CIN). A quantitative assessment of tumor genomes at the chromosomal level was newly introduced to reveal total DNA sizes and Scales of Genomic Alterations (SGA) for each cell line. Kasumi-1 and 6 derived from relapsed phases demonstrated high levels of SGA, implying that the level of SGA would reflect on the tumor progression and could serve as an index of CIN. Our results extend the leukemia cellular resources with an additional five cell lines and provide reference genome data with ethnic identities for the ten Kasumi cell lines.