Endocrine-Therapy-Resistant ESR1 Variants Revealed by Genomic Characterization of Breast-Cancer-Derived Xenografts
| Autor: | Shunqiang Li, Obi L. Griffith, Yiyu Dong, Jin Zhang, Laila Saied, Shuying Liu, Therese Giuntoli, Robert S. Fulton, Christopher G. Maher, Crystal Cooper, Jeremy Hoog, Wenbin Liu, Ron Bose, Austin Lin, Dave Larson, Robert J. Crowder, Chanpheng Phommaly, Xiaping He, Megha Shyam Kavuri, Rodrigo Franco Gonçalves, Yu Tao, Cynthia X. Ma, Caroline Bumb, Christopher A. Miller, Charles Lu, Ana M. Gonzalez-Angulo, John R. Edwards, Jeffrey F. Hiken, César Sánchez, Timothy J. Pluard, Dong Shen, Elaine R. Mardis, Michael Naughton, Li Ding, Gordon B. Mills, Rama Suresh, Reida G. McDowell, Joshua F. McMichael, R.T. Kitchens, Richard K. Wilson, Christopher E. Schlosberg, Sherri R. Davies, Jieya Shao, Aleix Prat, Loren S. Michel, Matthew J. Ellis, Rebecca Aft, Shaomeng Wang, Katherine DeSchryver, Jingqin Luo, Thomas B. Mooney, Michelle Harrison, Donna McEachern, Charles M. Perou, William E. Gillanders |
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| Přispěvatelé: | Universitat de Barcelona |
| Předmět: |
Genome instability
Somatic cell Molecular biology Breast Neoplasms Genomics Biology Genome Genomic Instability Translocation Genetic General Biochemistry Genetics and Molecular Biology Càncer de mama Mice 03 medical and health sciences 0302 clinical medicine Breast cancer Gene duplication Animals Humans Point Mutation RNA Neoplasm Allele lcsh:QH301-705.5 Alleles Adaptor Proteins Signal Transducing Neoplasm Staging 030304 developmental biology Biologia molecular Genetics 0303 health sciences Estradiol Estrogen Receptor alpha Gene Amplification YAP-Signaling Proteins Phosphoproteins Phenotype Neoplasm Proteins 3. Good health Transplantation Genòmica lcsh:Biology (General) Estudi de casos Drug Resistance Neoplasm 030220 oncology & carcinogenesis Heterografts Female Case studies Transcription Factors |
| Zdroj: | Recercat. Dipósit de la Recerca de Catalunya instname Dipòsit Digital de la UB Universidad de Barcelona Cell Reports, Vol 4, Iss 6, Pp 1116-1130 (2013) |
| Popis: | SummaryTo 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. |
| Databáze: | OpenAIRE |
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