科學家繪製出患者來源腫瘤異種移植物在傳代過程中拷貝數保守性的分析圖譜
作者：
小柯機器人發布時間：2021/1/9 21:24:49
美國傑克遜實驗室Jeffrey H. Chuang等研究人員合作繪製了患者來源腫瘤異種移植物在傳代過程中拷貝數保守性的分析圖譜。 這一研究成果發表在2021年出版的國際學術期刊《自然—遺傳學》上。
研究人員詳盡地分析了1,451個患者來源異種移植物（PDX）和509個PDX模型中匹配的患者腫瘤（PT）樣本中的拷貝數變化（CNA）。與基於基因表達的推斷相比，基於DNA測序和微陣列數據的CNA推斷顯示出更高的解析度和動態範圍，並且它們還顯示了從PT到後期傳遞PDX的強大CNA保守性。對130個結直腸癌和PT PDX早期/PDX晚期三聯症的CNA復發分析證實了高解析度的CNA保留。
研究人員沒有觀察到不同模型在PDX特異性CNA中癌症相關基因的顯著富集。此外，患者和PDX腫瘤之間的CNA差異可與患者內多區域樣本的差異相媲美。
這項研究表明，小鼠宿主不會驅動PDX的系統拷貝數進化。
據介紹，PDX是切除的人類腫瘤，然後被植入小鼠體內進行臨床前研究和治療測試。有研究已經提出，小鼠宿主會影響PDX植入和繁殖期間的腫瘤進化，從而影響人類癌症PDX建模的準確性。
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