The production of cytokines in response to DNA-damage events may be an important 
host defense response to help prevent the escape of pre-cancerous cells. The 
innate immune pathways involved in these events are known to be regulated by 
cellular molecules such as stimulator of interferon genes (STING), which 
controls type I interferon and pro-inflammatory cytokine production in response 
to the presence of microbial DNA or cytosolic DNA that has escaped from the 
nucleus. STING signaling has been shown to be defective in a variety of cancers, 
such as colon cancer and melanoma, actions that may enable damaged cells to 
escape the immunosurveillance system. Here, we report through examination of 
databases that STING signaling may be commonly suppressed in a greater variety 
of tumors due to loss-of-function mutation or epigenetic silencing of the 
STING/cGAS promoter regions. In comparison, RNA activated innate immune pathways 
controlled by RIG-I/MDA5 were significantly less affected. Examination of 
reported missense STING variants confirmed that many exhibited a 
loss-of-function phenotype and could not activate cytokine production following 
exposure to cytosolic DNA or DNA-damage events. Our data imply that the STING 
signaling pathway may be recurrently suppressed by a number of mechanisms in a 
considerable variety of malignant disease and be a requirement for cellular 
transformation.