Atypical teratoid rhabdoid tumor (ATRT) is a rare and aggressive type of cancer that primarily affects the central nervous system, especially in very young children. The cause of ATRT is fundamentally linked to genetic mutations, particularly involving genes that regulate how cells grow and divide.
The main culprit behind ATRT is the loss or mutation of a gene called SMARCB1 (also known as INI1 or hSNF5). This gene is a crucial part of a larger complex called the SWI/SNF chromatin remodeling complex, which controls how DNA is packaged and how genes are turned on or off. When SMARCB1 is mutated or deleted, this complex cannot function properly, leading to uncontrolled cell growth and tumor formation. In some cases, mutations in a related gene called SMARCA4 have also been found to cause ATRT, though these cases are less common and represent a distinct molecular subtype.
These genetic changes are usually not inherited but occur spontaneously in the cells of the brain or spinal cord during early development. The loss of SMARCB1 disrupts normal cell regulation, allowing immature cells to multiply uncontrollably and form tumors that contain a mix of different cell types, which is why the tumor is called “atypical” and “teratoid” (meaning it has various tissue types). The “rhabdoid” part refers to the tumor cells’ appearance under the microscope, which resemble rhabdomyoblasts, a type of muscle cell, although the tumor does not actually arise from muscle tissue.
Because these mutations affect fundamental mechanisms of gene regulation, ATRTs are highly aggressive and can grow rapidly. The tumors often have areas of necrosis (dead cells) and abnormal blood vessel formation, which contribute to their hemorrhagic and invasive nature.
In summary, ATRT is caused by genetic mutations that disable key tumor suppressor genes, mainly SMARCB1, leading to a failure in controlling cell growth and resulting in a highly malignant tumor composed of diverse cell types. These mutations typically arise early in life and are not inherited, making ATRT a devastating but genetically distinct pediatric brain tumor.
