小柯机器人

美国杰克逊实验室Jeffrey H. Chuang等研究人员合作绘制了患者来源肿瘤异种移植物在传代过程中拷贝数保守性的分析图谱。 这一研究成果发表在2021年出版的国际学术期刊《自然—遗传学》上。

研究人员详尽地分析了1,451个患者来源异种移植物（PDX）和509个PDX模型中匹配的患者肿瘤（PT）样本中的拷贝数变化（CNA）。与基于基因表达的推断相比，基于DNA测序和微阵列数据的CNA推断显示出更高的分辨率和动态范围，并且它们还显示了从PT到后期传递PDX的强大CNA保守性。对130个结直肠癌和PT PDX早期/PDX晚期三联症的CNA复发分析证实了高分辨率的CNA保留。

研究人员没有观察到不同模型在PDX特异性CNA中癌症相关基因的显著富集。此外，患者和PDX肿瘤之间的CNA差异可与患者内多区域样本的差异相媲美。

这项研究表明，小鼠宿主不会驱动PDX的系统拷贝数进化。

据介绍，PDX是切除的人类肿瘤，然后被植入小鼠体内进行临床前研究和治疗测试。有研究已经提出，小鼠宿主会影响PDX植入和繁殖期间的肿瘤进化，从而影响人类癌症PDX建模的准确性。

附：英文原文

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

Author: Xing Yi Woo, Jessica Giordano, Anuj Srivastava, Zi-Ming Zhao, Michael W. Lloyd, Roebi de Bruijn, Yun-Suhk Suh, Rajesh Patidar, Li Chen, Sandra Scherer, Matthew H. Bailey, Chieh-Hsiang Yang, Emilio Cortes-Sanchez, Yuanxin Xi, Jing Wang, Jayamanna Wickramasinghe, Andrew V. Kossenkov, Vito W. Rebecca, Hua Sun, R. Jay Mashl, Sherri R. Davies, Ryan Jeon, Christian Frech, Jelena Randjelovic, Jacqueline Rosains, Francesco Galimi, Andrea Bertotti, Adam Lafferty, Alice C. OFarrell, Elodie Modave, Diether Lambrechts, Petra ter Brugge, Violeta Serra, Elisabetta Marangoni, Rania El Botty, Hyunsoo Kim, Jong-Il Kim, Han-Kwang Yang, Charles Lee, Dennis A. Dean, Brandi Davis-Dusenbery, Yvonne A. Evrard, James H. Doroshow, Alana L. Welm, Bryan E. Welm, Michael T. Lewis, Bingliang Fang, Jack A. Roth, Funda Meric-Bernstam, Meenhard Herlyn, Michael A. Davies, Li Ding, Shunqiang Li, Ramaswamy Govindan, Claudio Isella, Jeffrey A. Moscow, Livio Trusolino, Annette T. Byrne, Jos Jonkers, Carol J. Bult, Enzo Medico, Jeffrey H. Chuang

Issue&Volume: 2021-01-07

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. 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.

DOI: 10.1038/s41588-020-00750-6

Source: https://www.nature.com/articles/s41588-020-00750-6

Nature Genetics：《自然—遗传学》，创刊于1992年。隶属于施普林格·自然出版集团，最新IF：41.307
官方网址：https://www.nature.com/ng/
投稿链接：https://mts-ng.nature.com/cgi-bin/main.plex