Representation of genomic intratumor heterogeneity in multi-region non-small cell lung cancer patient-derived xenograft models.

ABSTRACT: Patient-derived xenograft (PDX) models are widely used in cancer research. To investigate the genomic fidelity of non-small cell lung cancer PDX models, we established 48 PDX models from 22 patients enrolled in the TRACERx study. Multi-region tumor sampling increased successful PDX engraftment and most models were histologically similar to their parent tumor. Whole-exome sequencing enabled comparison of tumors and PDX models and we provide an adapted mouse reference genome for improved removal of NOD scid gamma (NSG) mouse-derived reads from sequencing data. PDX model establishment caused a genomic bottleneck, with models often representing a single tumor subclone. While distinct tumor subclones were represented in independent models from the same tumor, individual PDX models did not fully

SUBMITTER: Hynds RE 

PROVIDER: S-EPMC11143323 | biostudies-literature | 2024 May

REPOSITORIES: biostudies-literature