Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, Maryland.
Department of Urology, James Buchanan Brady Urological Institute, Johns Hopkins University School of Medicine, Baltimore, Maryland.
Mol Cancer Res. 2022 Jul 6;20(7):1013-1020. doi: 10.1158/1541-7786.MCR-21-0683.
A limited number of cell lines have fueled the majority of preclinical prostate cancer research, but their genomes remain incompletely characterized. Here, we utilized whole-genome linked-read sequencing for comprehensive characterization of phased mutations and rearrangements in the most commonly used cell lines in prostate cancer research including PC3, LNCaP, DU145, CWR22Rv1, VCaP, LAPC4, MDA-PCa-2b, RWPE-1, and four derivative castrate-resistant (CR) cell lines LNCaP_Abl, LNCaP_C42b, VCaP-CR, and LAPC4-CR. Phasing of mutations allowed determination of "gene-level haplotype" to assess whether genes harbored heterozygous mutations in one or both alleles. Phased structural variant analysis allowed identification of complex rearrangement chains consistent with chromothripsis and chromoplexy. In addition, comparison of parental and derivative CR lines revealed previously known and novel genomic alterations associated with the CR phenotype.
This study therefore comprehensively characterized phased genomic alterations in the commonly used prostate cancer cell lines, providing a useful resource for future prostate cancer research.
少数几种细胞系推动了大多数前列腺癌临床前研究，但它们的基因组仍未被完全描述。在这里，我们利用全基因组连接读取测序，对前列腺癌研究中最常用的细胞系（包括 PC3、LNCaP、DU145、CWR22Rv1、VCaP、LAPC4、MDA-PCa-2b、RWPE-1 以及四种衍生的去势抵抗（CR）细胞系 LNCaP_Abl、LNCaP_C42b、VCaP-CR 和 LAPC4-CR）中的相位突变和重排进行全面特征描述。突变的相位化允许确定“基因水平单倍型”，以评估基因是否在一个或两个等位基因中携带杂合突变。相位结构变异分析允许识别与染色体碎裂和染色体混合一致的复杂重排链。此外，比较亲本和衍生的 CR 系揭示了与 CR 表型相关的先前已知和新的基因组改变。
因此，本研究全面描述了常用前列腺癌细胞系中相位基因组改变，为未来的前列腺癌研究提供了有用的资源。
