Evaluation of molecular subtypes and clonal selection during establishment of patient-derived tumor xenografts from gastric adenocarcinoma
| Autor: | Vincent Vuaroqueaux, Isabella H. Wulur, Swee-Seong Wong, Manuel Landesfeind, Greg Donoho, Kerstin Klingner, Steven M. Bray, Han-Kwang Yang, Peter Bronsert, Anne-Lise Peille, Amit Aggarwal, Seong-Ho Kong, Woo Ho Kim, Bruno Zeitouni, Jason C. Ting, Christoph Reinhard, Nina Zanella, Heinz-Herbert Fiebig, Hyuk-Joon Lee |
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| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
endocrine system endocrine system diseases Medicine (miscellaneous) Translational research Biology digestive system Article General Biochemistry Genetics and Molecular Biology Immune compromised Efficacy 03 medical and health sciences Gastric adenocarcinoma 0302 clinical medicine Text mining Cancer models Cancer genetics lcsh:QH301-705.5 Tumor biology business.industry nutritional and metabolic diseases Histology 030104 developmental biology lcsh:Biology (General) 030220 oncology & carcinogenesis Cancer research Gastric cancer General Agricultural and Biological Sciences business hormones hormone substitutes and hormone antagonists Clonal selection |
| Zdroj: | Communications Biology, Vol 3, Iss 1, Pp 1-14 (2020) Communications Biology |
| ISSN: | 2399-3642 |
| DOI: | 10.1038/s42003-020-1077-z |
| Popis: | Patient-derived xenografts (PDX) have emerged as an important translational research tool for understanding tumor biology and enabling drug efficacy testing. They are established by transfer of patient tumor into immune compromised mice with the intent of using them as Avatars; operating under the assumption that they closely resemble patient tumors. In this study, we established 27 PDX from 100 resected gastric cancers and studied their fidelity in histological and molecular subtypes. We show that the established PDX preserved histology and molecular subtypes of parental tumors. However, in depth investigation of the entire cohort revealed that not all histological and molecular subtypes are established. Also, for the established PDX models, genetic changes are selected at early passages and rare subclones can emerge in PDX. This study highlights the importance of considering the molecular and evolutionary characteristics of PDX for a proper use of such models, particularly for Avatar trials. Peille et al. establish patient-derived xenografts (PDX) from gastric adenocarcinoma, expanding our knowledge on what subtypes can be developed into PDX models. Their extensive molecular characterization also reveals that PDX are subject to clonal selection in early passages, which is an important consideration for clinical studies. |
| Databáze: | OpenAIRE |
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