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五种常用子宫内膜癌细胞系的基因组特征分析。

Genomic characterization of five commonly used endometrial cancer cell lines.

机构信息

Department of Obstetrics and Gynecology, University of Iowa Carver College of Medicine, Iowa City, IA 52242, USA.

出版信息

Int J Oncol. 2020 Dec;57(6):1348-1357. doi: 10.3892/ijo.2020.5139. Epub 2020 Oct 21.

Abstract

Recently, the compilation of massive amounts of genetic and genomic information on a wide variety of human cancer types, collectively known as The Cancer Genome Atlas (TCGA), has revealed a wealth of descriptive classification schemes both within and between different types and sources of cancer. In endometrial cancer, TCGA analyses have produced a post hoc scheme composed of four clusters: DNA polymerase ε catalytic subunit A (POLE) ultra‑mutated (cluster 1), microsatellite instability (MSI) hypermutated (cluster 2), copy‑number low (endometrioid, cluster 3) and copy‑number high (serous‑like, cluster 4). Given that cultured cells are the pre‑clinical platform of cancer research, it was questioned how representative endometrial cancer cultured cell lines are in the context of TCGA‑driven classification scheme. To address this issue in endometrial cancer cell lines, the present study investigated five commonly used cell lines: Ishikawa, ECC‑1, Hec50co, KLE And RL95‑2. The histology, mutation profile, MutL homolog 1 promoter methylation, copy‑number variation, homologous recombination repair and microsatellite instability in each of these cell lines was assessed. The result of this characterization was that none of the cell lines fits neatly into any one of TCGA classes but are still useful models for groups of endometrial tumors. Furthermore, the contention that the ECC‑1 cell line is actually Ishikawa was addressed using additional data. It was confirmed that ECC‑1 cells likely no longer exist as ECC‑1 but that they are not exactly Ishikawa either. For this reason, ECC‑1 cells are suggested to be used in vitro but with this caveat in mind. Finally, we compiled a database of 127 endometrial cancer cell lines, including the five reported on here. The wide range of variation found in these cell lines highlights the need to further characterize these cells to select models that are more representative of the various histological and genomic aspects of endometrial cancer.

摘要

最近,对大量不同类型人类癌症的遗传和基因组信息进行了汇编,统称为癌症基因组图谱(TCGA),这揭示了丰富的描述性分类方案,包括不同类型和来源的癌症内部和之间的分类方案。在子宫内膜癌中,TCGA 分析产生了一个事后方案,由四个簇组成:DNA 聚合酶 ε 催化亚基 A(POLE)超突变(簇 1)、微卫星不稳定(MSI)高突变(簇 2)、拷贝数低(子宫内膜样,簇 3)和拷贝数高(类似浆液的,簇 4)。鉴于培养细胞是癌症研究的临床前平台,人们质疑在 TCGA 驱动的分类方案背景下,子宫内膜癌培养细胞系的代表性如何。为了解决子宫内膜癌细胞系中的这个问题,本研究调查了五种常用的细胞系:Ishikawa、ECC-1、Hec50co、KLE 和 RL95-2。评估了这些细胞系中的组织学、突变谱、MutL 同源物 1 启动子甲基化、拷贝数变异、同源重组修复和微卫星不稳定性。这种特征的结果是,没有一个细胞系完全适合 TCGA 中的任何一个类别,但对于子宫内膜肿瘤的某些群体仍然是有用的模型。此外,还使用其他数据解决了 ECC-1 细胞系实际上是 Ishikawa 的说法。确认 ECC-1 细胞可能不再以 ECC-1 的形式存在,但也不完全是 Ishikawa。出于这个原因,建议在体外使用 ECC-1 细胞,但要记住这一点。最后,我们编译了一个包含 127 种子宫内膜癌细胞系的数据库,包括这里报告的五种。这些细胞系中发现的广泛变异突出表明需要进一步对这些细胞进行特征描述,以选择更能代表子宫内膜癌各种组织学和基因组方面的模型。

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