Background Information

Studies show that 15-30% of melanomas are Nras driven and 60% of melanomas are Braf driven. Dr. Christin Burd's lab at The Ohio State University has developed a set of Nras-mutant mouse melanoma cell lines that complement a set of Braf cell lines developed by Marcus Bosenberg at Yale University.

The Need

Recent progress and successful application of immune-based therapies in cancer has increased the desire for immune-competent models to evaluate pre-clinical therapies. Immunocompetent genetically-engineered mouse models harboring discrete genetic drivers of melanoma are essential for studying potential immunotherapies, but are limited by the need to maintain colonies of multiple genotypes necessary to generate animals with the appropriate genetic backgrounds.

Tumor cell lines derived from inbred or congenic mice have been utilized for the study of tumor immune responses. The lines are easy to use, reproducible and experimental results can be readily attained. However, for many cancer types, the number of available cell lines for study is limited, the genetic drivers in the cells are often unclear and tumor growth characteristics are not ideal. Furthermore, mutational profiles among these tumors can be very different from their human counterparts. These considerations limit the utility and predictive value of using these models in isolation. The series of Nras mouse melanoma cell lines will help address many of these prior limitations.

The Technology

Fifteen Nras mouse melanoma cell lines have been developed. They were isolated from spontaneously arising melanomas in C57Bl/6 mice treated with ultraviolet B irradiation. Melanocytes in the donor animals all carry either an Nras61R mutation (TpN61R.62, TN61R.3, N61R.2-1, TN61R.9, TN61R.5, TN61R.14, TN61R.7, TN61R.4, TN61R1.1, TpN.62), an Nras61L mutation (TN61L.238), an Nras61K mutation (TN61K.242, TN61K.239.1, TN61K.239.2) or an Nras13R mutation (TN13R.283, TN13R.239). The TpN.62 cell line is also albino and null for p16INK4a.

Genotyping was performed to confirm that the cell lines contain the indicated Nras gene alteration. Whole exome sequencing was used to characterize other mutations arising as a result of tumorigenesis and/or UV irradiation.

Benefits/Advantages

The Nras mouse melanoma cell lines represent a valuable tool for tumor immunology and cancer biology, especially tractable for the evaluation and generation of new immunotherapies.