Genomic comparison of early-passage conditionally reprogrammed breast cancer cells to their corresponding primary tumors

作者：Akanksha Mahajan, Bruna M. Sugita, Anju Duttargi, Francisco Sáenz, Ewa Krawczyk, Justine N. McCutcheon, Aline Simoneti Fonseca, Bhaskar Kallakury, Paula R. Pohlmann, Yuriy Gusev, Luciane R. Cavalli · 发表于：PLoS ONE · 年份：2017 · DOI：10.1371/journal.pone.0186190 · 被引用次数：30 · 研究领域：Cancer Cells and Metastasis、Cancer Genomics and Diagnostics、Epigenetics and DNA Methylation

Conditionally reprogrammed cells (CRCs) are epithelial cells that are directly isolated from patients' specimens and propagated in vitro with feeder cells and a Rho kinase inhibitor. A number of these cells have been generated from biopsies of breast cancer patients, including ductal carcinoma in situ and invasive carcinomas. The characterization of their genomic signatures is essential to determine their ability to reflect the natural biology of their tumors of origin. In this study, we performed the genomic characterization of six newly established invasive breast cancer CRC cultures in comparison to the original patients' primary breast tumors (PBT) from which they derived. The CRCs and corresponding PBTs were simultaneously profiled by genome-wide array-CGH, targeted next generation sequencing and global miRNA expression to determine their molecular similarities in the patterns of copy number alterations (CNAs), gene mutations and miRNA expression levels, respectively. The CRCs' epithelial cells content and ploidy levels were also evaluated by flow cytometry. A similar level of CNAs was observed in the pairs of CRCs/PBTs analyzed by array-CGH, with >95% of overlap for the most frequently affected cytobands. Consistently, targeted next generation sequencing analysis showed the retention of specific somatic variants in the CRCs as present in their original PBTs. Global miRNA profiling closely clustered the CRCs with their PBTs (Pearson Correlation, ANOVA paired test, P<0.05...