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Conservation of copy number profiles during engraftment and passaging of patient-derived cancer xenografts
- Source :
- Nature Genetics, bioRxiv, PDXNET Consortium, EurOPDX Consortium, Alferez-Castro, D, Spence, K, Clarke, R & et al. 2021, ' Conservation of copy number profiles during engraftment and passaging of patient-derived cancer xenografts ', Nature Genetics, vol. 53, no. 1, pp. 86-99 . https://doi.org/10.1038/s41588-020-00750-6
- Publication Year :
- 2021
- Publisher :
- Springer Science and Business Media LLC, 2021.
-
Abstract
- 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.<br />Analysis of copy number alterations in 1,451 patient-derived xenografts (PDXs) and matched patient tumor samples shows strong conservation from patient tumors through late-passage PDXs and a lack of systematic copy number evolution driven by the mouse host.
- Subjects :
- endocrine system diseases
Microarray
gene amplification
Whole Exome Sequencing
Mice
0302 clinical medicine
Gene expression
Databases, Genetic
Gene duplication
Neoplasm Metastasis
Exome sequencing
Cancer
Regulation of gene expression
0303 health sciences
Manchester Cancer Research Centre
adult
adult, animal experiment, animal model, animal tissue, breast cancer, microarray, DNA sequencing engraftment, gene amplification, tumor, xenograft, tumor-related gene
Polymorphism, Single Nucleotide/genetics
3. Good health
Gene Expression Regulation, Neoplastic
030220 oncology & carcinogenesis
microarray
hormones, hormone substitutes, and hormone antagonists
tumor
endocrine system
DNA sequencing engraftment
animal experiment
DNA Copy Number Variations/genetics
Biology
digestive system
DNA sequencing
Article
animal tissue
03 medical and health sciences
breast cancer
Breast cancer
Genetics
medicine
Animals
Humans
xenograft
Gene
030304 developmental biology
Settore MED/04 - Patologia Generale
Microarray analysis techniques
animal model
ResearchInstitutes_Networks_Beacons/mcrc
tumor-related gene
medicine.disease
Xenograft Model Antitumor Assays
Computational biology and bioinformatics
Cancer research
Human cancer
Subjects
Details
- ISSN :
- 15461718 and 10614036
- Volume :
- 53
- Database :
- OpenAIRE
- Journal :
- Nature Genetics
- Accession number :
- edsair.doi.dedup.....636839fdd226e1a6cf4dfbb55f18ac93