Apr 11, 2016

The mutational landscape of EGFR-, MYC-, and Kras- driven genetically-engineered mouse models of lung adenocarcinoma

BioRxiv : the Preprint Server for Biology
David McFaddenHarold Varmus


Genetically-engineered mouse models (GEMMs) of cancer are increasingly being utilized to assess putative driver mutations identified by large scale sequencing of human cancer genomes. In order 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 EGFR, mutant Kras or by overexpression of MYC. Tumors from EGFR- and Kras- driven models exhibited respectively 0.02 and 0.07 non-synonymous mutations/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 somati...Continue Reading

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Mentioned in this Paper

Adenocarcinoma of Lung (Disorder)
Genomic Profile
Epidermal Growth Factor Receptor Activity

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