Please use this identifier to cite or link to this item:
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
Pluard, Timothy
Naughton, Michael
Bose, Ron
Keywords: Càncer de mama
Biologia molecular
Estudi de casos
Breast cancer
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:
It is part of: Cell Reports, 2013, vol. 4, num. 6, p. 1116-1130
Related resource:
ISSN: 2211-1247
Appears in Collections:Articles publicats en revistes (Medicina)

Files in This Item:
File Description SizeFormat 
662592.pdf3.41 MBAdobe PDFView/Open

This item is licensed under a Creative Commons License Creative Commons