Representation of genomic intratumor heterogeneity in multi-region non-small cell lung cancer patient-derived xenograft models
- Author(s)
- Hynds, RE; Huebner, A; Pearce, DR; Hill, MS; Akarca, AU; Moore, DA; Ward, S; Gowers, KHC; Karasaki, T; Al Bakir, M; Wilson, GA; Pich, O; Martinez-Ruiz, C; Hossain, ASMM; Pearce, SP; Sivakumar, M; Ben Aissa, A; Gronroos, E; Chandrasekharan, D; Kolluri, KK; Towns, R; Wang, K; Cook, DE; Bosshard-Carter, L; Naceur-Lombardelli, C; Rowan, AJ; Veeriah, S; Litchfield, K; Crosbie, PAJ; Dive, C; Quezada, SA; Janes, SM; Jamal-Hanjani, M; Marafioti, T; TRACERx Consortium; McGranahan, N; Swanton, C;
- Journal Title
- Nature Communications
- Publication Type
- Research article
- 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 recapitulate intratumor heterogeneity. On-going genomic evolution in mice contributed modestly to the genomic distance between tumors and PDX models. Our study highlights the importance of considering primary tumor heterogeneity when using PDX models and emphasizes the benefit of comprehensive tumor sampling.
- Publisher
- Springer Nature
- Keywords
- *Carcinoma, Non-Small-Cell Lung/genetics/pathology; Humans; Animals; *Lung Neoplasms/genetics/pathology; Mice; *Mice, Inbred NOD; *Mice, SCID; *Genetic Heterogeneity; Female; Exome Sequencing; Genomics/methods; Male; Xenograft Model Antitumor Assays; Heterografts; Disease Models, Animal; Aged; Middle Aged
- Department(s)
- Laboratory Research
- PubMed ID
- 38821942
- Publisher's Version
- https://doi.org/10.1038/s41467-024-47547-3
- Open Access at Publisher's Site
https://doi.org/10.1038/s41467-024-47547-3- Terms of Use/Rights Notice
- Refer to copyright notice on published article.
Creation Date: 2025-04-24 05:44:29
Last Modified: 2025-04-24 05:45:33