Whole Exome Sequencing Reveals Similarities Between Asbestos-induced Mesothelioma Mice and Human Patients

Whole Exome Sequencing Reveals Similarities Between Asbestos-induced Mesothelioma Mice and Human Patients

Whole exome sequencing of asbestos-induced mouse models of malignant mesothelioma (MM) is a genuine representation of human mesothelioma and is a valuable tool for further research into the development and treatment of this disease, new research shows.

The study, “Whole exome sequencing of an asbestos-induced wild-type murine model of malignant mesothelioma,” was published in the journal BMC Cancer.

Malignant mesothelioma is a cancer that is caused by DNA damage in mesothelial cells. It occurs primarily by exposure of an individual to asbestos. There can be a long latency period between when an individual is exposed to asbestos and the development of mesothelioma, usually between 30-50 years.

Like humans, asbestos causes development of mesothelioma in mice as well. In fact, asbestos-induced mesothelioma in mice is almost identical to humans in pathology, immunology, and clinical symptoms, which is rare in most cancer mouse models. While many studies have employed the use of these mice as a tool to determine potential mesothelioma therapies, there is no study that outlines the genetic lesions of MM in this mouse model.

So far, many genetically engineered mice have been used to study specific mutations that are involved in mesothelioma, such as Cdkn2a gene mutations. However, while these mouse models can be useful, they don’t give the whole picture of the tumor.

Little is known about the mutational landscape of asbestos-induced MM in mouse models. Therefore, researchers at the University of Western Australia set out to characterize the DNA mutations that underlie this tumor.

Asbestos was injected into the abdomen of mice, then researchers conducted whole exome sequencing, which characterizes gene expression. They were able to obtain 15 different mouse tumor cell lines from three different strains of mice.

By conducting whole exome sequencing of these tumors, researchers showed that mesotheliomas from these mice had consistent loss of Cdkn2a across all of the asbestos-induced tumors. This is similar to the human mesothelioma tumor as more than 70 percent of malignant mesothlioma cases have a loss of CDKN2A.

Despite the absence of other human mesothlioma mutations, the loss of the Cdkn2a gene appears to be enough to cause development of asbestos-induced mesothlioma.

One of the exciting features of this mouse model is that it displays a high proportion of chromosomal loss compared to gain, which is also prominent in human mesothlioma. There was also an increased expression of c-Myc, which is also upregulated in human mesothlioma.

In addition, the rate of mutation between human mesothlioma and asbestos-induced mouse mesothlioma are comparable. And, genes involved in the Jak-STAT and MAPK pathway were also altered in the mouse model, similar to human mesothlioma.

Taken together, the results of this study support the use of this wild-type mouse model of asbestos-induced malignant mesothlioma as a tool for studying human disease.

One comment

Leave a Comment

Your email address will not be published.