研究发现一种改进的癌症模型

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传统小鼠癌症模型是通过将一种致癌基因转移进小鼠胚胎中做成的。转移后实验鼠会患癌症，但所患癌症却不会表现在人体中所发现的明显的基因组不稳定性。人类癌症一般与很多基因变异有关，其中有些是致癌的，有些是正在形成中的疾病的构成部分，而有些则是偶然发生的。现在，研究人员已经培养出一个能够模仿人类癌症中基因组稳定水平的新的小鼠模型。该研究成果发表在最新一期的《Nature》杂志上。

研究人员是把能够引起染色体不稳定的遗传要素用基因工程方法转移进易患淋巴癌的小鼠体内而培养出这一小鼠模型的，该模型在很多方面与人类疾病非常相似，包括基因FBXW7 和 PTEN发生删除和突变等。这种改进的癌症模型对于研究人类癌症的发生机制具有重要意义。


FIGURE 1. The TKO model.
a, Kaplan–Meier curve of thymic lymphoma-free survival for G3–G4 TKO mice with varying Trp53 dosage. b, Trp53 loss of heterozygosity assessed by PCR. N, normal; T, tumour. c, Representative FACS profile of a TKO tumour with CD4 and CD8 cell surface marker antibodies. d, Representative SKY images from metaphase spreads from G0 (upper panel) and G1–G4 (lower panel) lymphomas. e, Quantification of cytogenetic aberrations (recurrences) detected by SKY in G0 (blue) and G1–G4 (red) thymic lymphomas. Darker portion of column indicates proportion of non-reciprocal translocations; lighter portion indicates dicentric/robertsonian-like rearrangements. f, Recurrence plot of CNAs defined by array-CGH for 35 TKO lymphomas. The x axis shows the physical location of each chromosome. The percentage of tumours harbouring gains (dark red, log2 0.3), amplifications (bright red, log2 0.6), losses (green, log2 -0.3), and deletions (dark green, log2 -0.6) for each locus is depicted. Locations of physiologically relevant CNAs at Tcrb, Tcra/Tcrd and Tcrg (arrows), and Notch1 and Pten (asterisks) are indicated.





原文出处：

Nature Volume 447 Number 7147

Chromosomally unstable mouse tumours have genomic alterations similar to diverse human cancers p966
Richard S. Maser, Bhudipa Choudhury, Peter J. Campbell, Bin Feng, Kwok-Kin Wong, Alexei Protopopov, Jennifer O'Neil, Alejandro Gutierrez, Elena Ivanova, Ilana Perna, Eric Lin, Vidya Mani, Shan Jiang, Kate McNamara, Sara Zaghlul, Sarah Edkins, Claire Stevens, Cameron Brennan, Eric S. Martin, Ruprecht Wiedemeyer, Omar Kabbarah, Cristina Nogueira, Gavin Histen, Jon Aster, Marc Mansour, Veronique Duke, Letizia Foroni, Adele K. Fielding, Anthony H. Goldstone, Jacob M. Rowe, Yaoqi A. Wang, A. Thomas Look, Michael R. Stratton, Lynda Chin, P. Andrew Futreal & Ronald A. DePinho