Identifying Phased Mutations and Complex Rearrangements in Human Prostate Cancer Cell Lines through Linked-Read Whole-Genome Sequencing.

Autor:	Pham MT; 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.; Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, Maryland.; Cellular and Molecular Medicine Graduate Program, Johns Hopkins University School of Medicine, Baltimore, Maryland., Gupta A; Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, Maryland., Gupta H; Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, Maryland.; Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, Maryland., Vaghasia A; Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, Maryland.; Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, Maryland.; Cellular and Molecular Medicine Graduate Program, Johns Hopkins University School of Medicine, Baltimore, Maryland., Skaist A; Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, Maryland., Garrison MA; Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, Maryland.; Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, Maryland.; Department of Molecular Biology and Genetics, Johns Hopkins University School of Medicine, Baltimore, Maryland.; Biochemistry, Cellular and Molecular Biology Graduate Program, Johns Hopkins University School of Medicine, Baltimore, Maryland., Coulter JB; Department of Urology, James Buchanan Brady Urological Institute, Johns Hopkins University School of Medicine, Baltimore, Maryland.; Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, Maryland., Haffner MC; Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, Maryland.; Division of Human Biology and Clinical Research, Fred Hutchinson Cancer Research Center, Seattle, Washington.; Department of Pathology, University of Washington, Seattle, Washington., Zheng SL; Program for Personalized Cancer Care, NorthShore University HealthSystem, Evanston, Illinois., Xu J; Program for Personalized Cancer Care, NorthShore University HealthSystem, Evanston, Illinois., DeStefano Shields C; Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, Maryland.; Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, Maryland., Isaacs WB; 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.; Cellular and Molecular Medicine Graduate Program, Johns Hopkins University School of Medicine, Baltimore, Maryland., Wheelan SJ; Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, Maryland.; Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, Maryland.; Department of Molecular Biology and Genetics, Johns Hopkins University School of Medicine, Baltimore, Maryland., Nelson WG; Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, Maryland.; Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, Maryland.; Cellular and Molecular Medicine Graduate Program, Johns Hopkins University School of Medicine, Baltimore, Maryland., Yegnasubramanian S; Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, Maryland.; Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, Maryland.; Cellular and Molecular Medicine Graduate Program, Johns Hopkins University School of Medicine, Baltimore, Maryland.
Jazyk:	angličtina
Zdroj:	Molecular cancer research : MCR [Mol Cancer Res] 2022 Jul 06; Vol. 20 (7), pp. 1013-1020.
DOI:	10.1158/1541-7786.MCR-21-0683
Abstrakt:	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. Implications: 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. (©2022 The Authors; Published by the American Association for Cancer Research.)
Databáze:	MEDLINE
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