Nat Commun:識別的最佳卵巢癌模型

刊登在近日國際雜誌Nature Communications上的一項基因組分析顯示，用於研究工作的一些最流行的卵巢癌細胞系可能並不是卵巢癌的好模型。

從臨床腫瘤樣本獲得的癌細胞系經常用在癌症研究中，並使我們對癌症生物學有了很多新認識。Nikolaus Schultz和他的研究團隊分析了來自兩個大型基因測序項目的可以公開獲得的數據集，這兩個項目分別是：「癌症基因組圖譜」——確定臨床卵巢癌樣本的基因組特徵；「癌細胞系百科全書」——包含用於研究工作的大約1000個癌細胞系的相似數據。

Schultz的團隊對這些數據彼此之間進行了匹配，並根據大約50個卵巢癌細胞系與來自「高等級漿液性卵巢癌」 (HGSOC) 患者的臨床樣本的基因組相似性對它們進行了排序。他們發現，兩個最流行的卵巢癌細胞系（佔所有已發表的關於HGSOC的研究論文的60%）並不是非常像HGSOC，而12個最適合的卵巢癌細胞系僅用在1%的已發表研究論文中。

該研究提供了一個方法論框架，這個框架也許還可應用於其他細胞系和不同類型的癌症，以便評估它們作為研究工具是否合適。

Evaluating cell lines as tumour models by comparison of genomic profiles

Silvia Domcke, Rileen Sinha, Douglas A. Levine, Chris Sander & Nikolaus Schultz

Cancer cell lines are frequently used as in vitro tumour models. Recent molecular profiles of hundreds of cell lines from The Cancer Cell Line Encyclopedia and thousands of tumour samples from the Cancer Genome Atlas now allow a systematic genomic comparison of cell lines and tumours. Here we analyse a panel of 47 ovarian cancer cell lines and identify those that have the highest genetic similarity to ovarian tumours. Our comparison of copy-number changes, mutations and mRNA expression profiles reveals pronounced differences in molecular profiles between commonly used ovarian cancer cell lines and high-grade serous ovarian cancer tumour samples. We identify several rarely used cell lines that more closely resemble cognate tumour profiles than commonly used cell lines, and we propose these lines as the most suitable models of ovarian cancer. Our results indicate that the gap between cell lines and tumours can be bridged by genomically informed choices of cell line models for all tumour types.