Evaluation of molecular subtypes and clonal selection during establishment of patient-derived tumor xenografts from gastric adenocarcinoma

胃腺癌患者肿瘤异种移植模型建立过程中分子亚型及克隆选择的评估

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作者:Anne-Lise Peille #, Vincent Vuaroqueaux #, Swee-Seong Wong, Jason Ting, Kerstin Klingner, Bruno Zeitouni, Manuel Landesfeind, Woo Ho Kim, Hyuk-Joon Lee, Seong-Ho Kong, Isabella Wulur, Steven Bray, Peter Bronsert, Nina Zanella, Greg Donoho, Han-Kwang Yang, Heinz-Herbert Fiebig, Christoph Reinhard, Am

Abstract

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.

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