No one knows what causes a child to develop a DIPG tumor. Some cancers are caused by particular genes that a person inherited from his parents, but there is no evidence that links DIPG to any specific inherited genes. Other cancers are caused by environmental factors (such as smoking or exposure to chemicals or radiation), but there is no evidence that links DIPG to any environmental factor.

Recent research has suggested that DIPG tumor formation may be linked to brain development. These studies suggest that the disease process may be influenced by particular cells that are present in the highest concentrations while the brain is developing. The theory that DIPG is linked to brain development is also supported by the fact that DIPG most often occurs during middle childhood (ages 5-10), a period in which the brain develops significantly. It would also explain why adults do not commonly get DIPG tumors.

Recent research has also identified genetic and epigenetic mutations that are present in DIPG tumors. But more research is needed to determine which of these mutations cause the DIPG tumor to form, and how they do that. And more research is needed to determine what causes the mutations to occur in the first place.