Conservation of copy number profiles during engraftment and passaging of patient-derived cancer xenografts

PDXNET Consortium, EurOPDX Consortium, Dennis Alferez-Castro, Katherine Spence, Robert Clarke, et al.

Research output: Contribution to journalArticlepeer-review

75 Downloads (Pure)


Patient-derived xenografts (PDXs) are resected human tumors engrafted into mice for preclinical studies and therapeutic testing. It has been proposed that the mouse host affects tumor evolution during PDX engraftment and propagation, affecting the accuracy of PDX modeling of human cancer. Here, we exhaustively analyze copy number alterations (CNAs) in 1,451 PDX and matched patient tumor (PT) samples from 509 PDX models. CNA inferences based on DNA sequencing and microarray data displayed substantially higher resolution and dynamic range than gene expression-based inferences, and they also showed strong CNA conservation from PTs through late-passage PDXs. CNA recurrence analysis of 130 colorectal and breast PT/PDX-early/PDX-late trios confirmed high-resolution CNA retention. We observed no significant enrichment of cancer-related genes in PDX-specific CNAs across models. Moreover, CNA differences between patient and PDX tumors were comparable to variations in multiregion samples within patients. Our study demonstrates the lack of systematic copy number evolution driven by the PDX mouse host.
Original languageEnglish
Pages (from-to)86-99
Number of pages14
JournalNature Genetics
Issue number1
Publication statusPublished - 7 Jan 2021


  • Animals
  • DNA Copy Number Variations/genetics
  • Databases, Genetic
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Mice
  • Neoplasm Metastasis
  • Polymorphism, Single Nucleotide/genetics
  • Whole Exome Sequencing
  • Xenograft Model Antitumor Assays

Research Beacons, Institutes and Platforms

  • Manchester Cancer Research Centre


Dive into the research topics of 'Conservation of copy number profiles during engraftment and passaging of patient-derived cancer xenografts'. Together they form a unique fingerprint.

Cite this