CNR1 and CNR2 Cannabinoid Receptor Mutations in Cancer Cells

Cannabinoids, including the psychoactive D9-tetrahydrocannabinol (THC) and the non-psychoactive cannabidiol (CBD), interact with receptors within the endocannabinoid system. The major receptors within this system are CNR1 (cannabinoid receptor 1) and CNR2 (cannabinoid receptor 2), which are both seven-transmembrane G-protein-coupled receptors. In this report, we used the Catalogue of Somatic Mutations in Cancers (COSMIC) to map and analyze mutations arising in CNR1 and CNR2. The goal was to determine if any trends or signatures could be identified. We identified several mutations in both CNR1 and CNR2. In silico 3D structure of proteins reveals that these mutations cluster on the intracellular regions of CNR1 and CNR2, and certain residues may be able to destabilize the interaction with the G-alpha protein due to their close proximity. mRNA expression showed that CNR1 and CNR2 are within normal expression levels in most cancer types except kidney, where there is a tendency towards over-expression. Neither CNR1 nor CNR2 is a driver gene, and our analysis shows that mutations in cancer cells are deactivating (e.g., loss of function).