Abstract
Chromosomal changes are important factors in the development of human cancers, leading to the creation of gene fusions that can be targeted by therapeutic treatments. One such gene fusion is EML4-ALK, which results from an inversion on chromosome 1 and is found in a subset of non-small cell lung cancers. This gene fusion is clinically significant because it makes the cancer cells sensitive to ALK inhibitors. However, modeling these genetic events in mice has been difficult and requires complex manipulation of the germ line. This study presents an efficient method of inducing specific chromosomal changes in vivo using viral-mediated delivery of the CRISPR/Cas9 system to somatic cells of adult animals. The method was used to create a mouse model of EML4-ALK-driven lung cancer. The resulting tumors consistently exhibited EML4-ALK inversion, expressed the EML4-ALK fusion gene and had molecular features of human NSCLCs and react to handling with ALK inhibitors. The capacity to simulate human malignancies in mice is substantially improved by this method.
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