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|Title:||Endocrine-Therapy-Resistant ESR1 Variants Revealed by Genomic Characterization of Breast-Cancer-Derived Xenografts|
Prat Aparicio, Aleix
Griffith, Obi L.
Fulton, Robert S.
McMichael, Joshua F.
Hiken, Jeffrey F.
Kitchens, Robert T.
Davies, Sherri R.
Kavuri, Megha Shyam
Dong, Yi Yu
|Keywords:||Càncer de mama|
Estudi de casos
|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|
|Appears in Collections:||Articles publicats en revistes (Medicina)|
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