Patient-derived xenografts of central nervous system metastasis reveal expansion of aggressive minor clones.

ABSTRACT:

Background

The dearth of relevant tumor models reflecting the heterogeneity of human central nervous system metastasis (CM) has hindered development of novel therapies.

Methods

We established 39 CM patient-derived xenograft (PDX) models representing the histological spectrum, and performed phenotypic and multi-omic characterization of PDXs and their original patient tumors. PDX clonal evolution was also reconstructed using allele-specific copy number and somatic variants.

Results

PDXs retained their metastatic potential, with flank-implanted PDXs forming spontaneous metastases in multiple organs, including brain, and CM subsequent to intracardiac injection. PDXs also retained the histological and molecular profiles of the original patient tumors, including retention o

SUBMITTER: Tew BY 

PROVIDER: S-EPMC6954401 | biostudies-literature | 2020 Jan

REPOSITORIES: biostudies-literature