TY - JOUR
T1 - Identifying Phased Mutations and Complex Rearrangements in Human Prostate Cancer Cell Lines through Linked-Read Whole-Genome Sequencing
AU - Pham, Minh Tam
AU - Gupta, Anuj
AU - Gupta, Harshath
AU - Vaghasia, Ajay
AU - Skaist, Alyza
AU - Garrison, McKinzie A.
AU - Coulter, Jonathan B.
AU - Haffner, Michael C.
AU - Lilly Zheng, S.
AU - Xu, Jianfeng
AU - Shields, Christina De Stefano
AU - Isaacs, William B.
AU - Wheelan, Sarah J.
AU - Nelson, William G.
AU - Yegnasubramanian, Srinivasan
N1 - Publisher Copyright:
© 2022 The Authors; Published by the American Association for Cancer Research
PY - 2022/7
Y1 - 2022/7
N2 - 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.
AB - 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.
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U2 - 10.1158/1541-7786.MCR-21-0683
DO - 10.1158/1541-7786.MCR-21-0683
M3 - Article
C2 - 35452513
AN - SCOPUS:85134360357
SN - 1541-7786
VL - 20
SP - 1013
EP - 1020
JO - Molecular Cancer Research
JF - Molecular Cancer Research
IS - 7
ER -