Xenografting of advanced stage breast cancer preserves the genomic and clonal architecture and captures luminal tumors harboring mutations and gene rearrangements in ESR1

ABSTRACT: End-stage breast cancers are clonally heterogeneous and harbor many poorly-understood treatment resistance mechanisms. We therefore established multiple Patient-Derived-Xenograft (PDX) models to study genomic events driving advanced disease. Comparative whole-genome sequencing of paired primary tumors and their PDX models demonstrated that PDX retain the vast majority of the structural variations and copy number aberrations seen within the originating tumor, and with high fidelity. Variant allele fractions (VAF) were preserved, even for rare mutations. Clonal representation is therefore a transplantable phenotype, indicating that genomic heterogeneity can be regulated in a tumor-autonomous mechanism, indifferent to host immune status. Mutations and gene rearrangements were documented

ORGANISM(S): Homo sapiens

SUBMITTER: Li S 

PROVIDER: S-ECPF-GEOD-46604 | biostudies-other | 2013 Sep

REPOSITORIES: biostudies-other