Diffuse Intrinsic Pontine Glioma (DIPG) is a rare and aggressive tumor that forms in the pons, a part of the brainstem controlling functions like breathing, heartbeat, and balance. This cancer primarily affects children, most often between the ages of five and ten. Given its location and rapid growth, it is a difficult pediatric cancer to manage. For families receiving this diagnosis, a primary question is about its origin and whether the condition is inherited or runs in families.
The Role of Genetic Mutations in DIPG
DIPG is fundamentally a disease rooted in genetic changes. It arises when the DNA within a single cell in the brainstem accumulates errors, known as mutations. These mutations disrupt the cell’s normal instructions, causing it to multiply without restraint and form a diffuse tumor that infiltrates the pons.
The genetic errors are almost always acquired spontaneously during a child’s development, meaning they are not inherited from a parent. The mutations happen randomly in one cell at a specific point in time, rather than being present in the family’s genetic makeup.
This distinction is important for understanding why DIPG is not considered a hereditary disease. The genetic events that trigger the tumor are confined to the tumor cells themselves and are not present in the other cells of the child’s body, nor can they be passed to future generations.
Somatic Versus Hereditary Cancer Mutations
To understand why DIPG is not passed through families, it is helpful to distinguish between two categories of genetic mutations. The changes that cause DIPG are known as somatic mutations, which occur in a single body cell after conception and are not inherited. Think of it as a random typo that appears in just one copy of a book; it was not in the original manuscript and will not be in any other copies.
Somatic mutations are restricted to the tumor and any cells that descend from the original mutated cell. Because they are not in the sperm or egg cells, they cannot be passed on to offspring.
In contrast, hereditary cancer is caused by germline mutations. These are inherited from a parent and are present in every cell of a person’s body. Germline mutations lead to familial cancer syndromes, where the risk of developing certain cancers is passed down through generations. DIPG does not fit this profile.
Key Genetic Alterations Found in Tumors
Scientific research has identified specific somatic mutations that are characteristic of DIPG tumors. In approximately 80% of cases, a mutation known as H3K27M is present. This mutation affects histone genes, which create proteins that act like spools for packaging DNA within a cell’s nucleus. When a histone gene is mutated, this packaging process is disrupted, altering gene expression and leading to abnormal cell growth.
While the H3K27M mutation is the most common driver, other genetic alterations are also found. Mutations in a gene called ACVR1 are frequently identified, often alongside the H3K27M mutation. The ACVR1 gene is involved in cell growth, and mutations can lock it into an “on” state, promoting uncontrolled proliferation.
Another gene often implicated is TP53, which functions as a tumor suppressor. Its job is to recognize DNA damage and halt cell division for repairs or, if the damage is too severe, trigger cell death. When TP53 is mutated, this protective mechanism fails, allowing cells with genetic flaws to survive and multiply.
Family History and Associated Risk
A diagnosis of DIPG does not increase the cancer risk for other family members. Since the mutations are somatic and confined to the tumor, there is no established mechanism for the condition to be passed to siblings, parents, or future offspring. The spontaneous nature of these mutations means the occurrence of DIPG in one child is not a predictor of risk for others in the family.
In very rare instances, some hereditary cancer predisposition syndromes can increase the overall risk of developing brain tumors. For example, Li-Fraumeni syndrome, caused by a germline mutation in the TP53 gene, makes an individual more susceptible to various cancers. Neurofibromatosis type 1 is another rare genetic condition associated with a higher risk of brain stem gliomas.
However, these syndromes account for an extremely small fraction of pediatric brain tumor cases, and DIPG is not considered a feature of these conditions. For the overwhelming majority of families, the development of DIPG is an isolated event with no connection to family history. There are also no known environmental exposures or lifestyle factors that have been confirmed to cause DIPG.