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http://hdl.handle.net/2445/102127
Title: | Endocrine-Therapy-Resistant ESR1 Variants Revealed by Genomic Characterization of Breast-Cancer-Derived Xenografts |
Author: | Li, Shunqiang Shen, Dong Shao, Jieya Crowder, Robert Liu, Wenbin Prat Aparicio, Aleix He, Xiaping Liu, Shuying Hoog, Jeremy Lu, Charles Ding, Li Griffith, Obi L. Miller, Christopher Larson, Dave Fulton, Robert S. Harrison, Michelle Mooney, Tom McMichael, Joshua F. Luo, Jingqin Tao, Yu Goncalves, Rodrigo Schlosberg, Christopher Hiken, Jeffrey F. Saied, Laila Sanchez, Cesar Giuntoli, Therese Bumb, Caroline Cooper, Crystal Kitchens, Robert T. Lin, Aaustin Phommaly, Chanpheng Davies, Sherri R. Zhang, Jim Kavuri, Megha Shyam McEachern, Donna Dong, Yi Yu Ma, Cynthia X. Pluard, Timothy Naughton, Michael Bose, Ron |
Keywords: | Càncer de mama Genòmica Biologia molecular Estudi de casos Breast cancer Genomics Molecular biology Case studies |
Issue Date: | 19-Sep-2013 |
Publisher: | Elsevier |
Abstract: | To characterize patient-derived xenografts (PDXs) for functional studies, we made whole-genome comparisons with originating breast cancers representative of the major intrinsic subtypes. Structural and copy number aberrations were found to be retained with high fidelity. However, at the single-nucleotide level, variable numbers of PDX-specific somatic events were documented, although they were only rarely functionally significant. Variant allele frequencies were often preserved in the PDXs, demonstrating that clonal representation can be transplantable. Estrogen-receptor-positive PDXs were associated with ESR1 ligand-binding-domain mutations, gene amplification, or an ESR1/YAP1 translocation. These events produced different endocrine-therapy-response phenotypes in human, cell line, and PDX endocrine-response studies. Hence, deeply sequenced PDX models are an important resource for the search for genome-forward treatment options and capture endocrine-drug-resistance etiologies that are not observed in standard cell lines. The originating tumor genome provides a benchmark for assessing genetic drift and clonal representation after transplantation. |
Note: | Reproducció del document publicat a: http://dx.doi.org/10.1016/j.celrep.2013.08.022 |
It is part of: | Cell Reports, 2013, vol. 4, num. 6, p. 1116-1130 |
URI: | http://hdl.handle.net/2445/102127 |
Related resource: | http://dx.doi.org/10.1016/j.celrep.2013.08.022 |
ISSN: | 2211-1247 |
Appears in Collections: | Articles publicats en revistes (Medicina) |
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