scholarly journals Studying lung cancer progression: insights from genetically engineered mouse models of cancer

2015 ◽  
Vol 4 (4) ◽  
pp. 155-157
Author(s):  
Sarah Neidler ◽  
Daniel J Murphy
Keyword(s):  
Lung Cancer ◽  
Mouse Models ◽  
Cancer Progression ◽  
Genetically Engineered ◽  
Genetically Engineered Mouse Models ◽  
Mouse Models Of Cancer

scholarly journals Mutational landscape of EGFR-, MYC-, and Kras-driven genetically engineered mouse models of lung adenocarcinoma

2016 ◽  
Vol 113 (42) ◽  
pp. E6409-E6417 ◽  
Author(s):  
David G. McFadden ◽  
Katerina Politi ◽  
Arjun Bhutkar ◽  
Frances K. Chen ◽  
Xiaoling Song ◽  
...  
Keyword(s):  
Lung Adenocarcinoma ◽  
Mouse Models ◽  
Cancer Progression ◽  
Large Scale ◽  
Human Cancer ◽  
Genetically Engineered ◽  
Model Systems ◽  
Driver Mutations ◽  
Genetic Profile ◽  
Genetically Engineered Mouse Models

Genetically engineered mouse models (GEMMs) of cancer are increasingly being used to assess putative driver mutations identified by large-scale sequencing of human cancer genomes. To accurately interpret experiments that introduce additional mutations, an understanding of the somatic genetic profile and evolution of GEMM tumors is necessary. Here, we performed whole-exome sequencing of tumors from three GEMMs of lung adenocarcinoma driven by mutant epidermal growth factor receptor (EGFR), mutant Kirsten rat sarcoma viral oncogene homolog (Kras), or overexpression of MYC proto-oncogene. Tumors from EGFR- and Kras-driven models exhibited, respectively, 0.02 and 0.07 nonsynonymous mutations per megabase, a dramatically lower average mutational frequency than observed in human lung adenocarcinomas. Tumors from models driven by strong cancer drivers (mutant EGFR and Kras) harbored few mutations in known cancer genes, whereas tumors driven by MYC, a weaker initiating oncogene in the murine lung, acquired recurrent clonal oncogenic Kras mutations. In addition, although EGFR- and Kras-driven models both exhibited recurrent whole-chromosome DNA copy number alterations, the specific chromosomes altered by gain or loss were different in each model. These data demonstrate that GEMM tumors exhibit relatively simple somatic genotypes compared with human cancers of a similar type, making these autochthonous model systems useful for additive engineering approaches to assess the potential of novel mutations on tumorigenesis, cancer progression, and drug sensitivity.

scholarly journals Rapid Validation of Cancer Genes and Drug Targets in Genetically Engineered Mouse Models of Cancer

2013 ◽  
Vol 24 ◽  
pp. i7
Author(s):  
I.J. Huijbers ◽  
R. Bin Ali ◽  
C. Pritchard ◽  
M. Cozijnsen ◽  
N. Proost ◽  
...  
Keyword(s):  
Mouse Models ◽  
Drug Targets ◽  
Genetically Engineered ◽  
Cancer Genes ◽  
Genetically Engineered Mouse Models ◽  
Mouse Models Of Cancer
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