Diffuse Intrinsic Pontine Glioma
Diffuse Intrinsic Pontine Glioma (D.I.P.G.) is a tumor located in the pons of the brain stem.
The brain stem is the bottom most portion of the brain, connecting the cerebrum with the spinal cord. The majority of brain stem tumours occur in the pons, are diffusely infiltrating (they grow amidst the nerves), and therefore are not able to be surgically removed.
Pontine gliomas are malignant (cancerous) tumours that originate from the part of the brain known as the brain stem (pons). They develop from cells called astrocytes. Astrocytomas are the most common type of glioma. You will often hear the terms astrocytoma and glioma used interchangeably. In children, 80% of brain stem tumours are pontine gliomas.
If a biopsy is carried out they are usually found to be high grade gliomas and are classified according to the grade of aggressiveness (how quickly they grow) as either anaplastic astrocytomas (grade III) or glioblastoma multiforme (GBM). These tumours grow amongst the normal nerve cells of the brain stem making them impossible to remove surgically as the brain stem is a vital area of the brain that controls many body functions.
Who gets pontine glioma?
Less than 40 children a year develop pontine glioma in the UK. This is around 10-15% of all childhood brain tumours. They rarely occur in adults. Like most brain tumours, the cause of pontine gliomas is unknown.
Cytogenetic Characteristics of Diffuse Intrinsic Pontine Gliomas
The genomic characteristics of DIPGs appear to differ from those of most other pediatric high-grade gliomas and from those of adult high-grade gliomas. A number of chromosomal and genomic abnormalities have been reported for DIPG, including the following:
Histone H3 genes: Approximately 80% of DIPG tumors have a mutation in a specific amino acid in the histone H3.1 (H3F3A) or H3.3 (HIST1H3B) genes. These same mutations are observed in pediatric high-grade gliomas at other midline locations but are uncommon in cortical pediatric high-grade gliomas and in adult high-grade gliomas.
Activin A receptor, type I (ACVR1) gene: Approximately 20% of DIPG cases have activating mutations in the ACVR1 gene, with most occurring concurrently with H3.3 mutations. Germline mutations in ACVR1 cause the autosomal dominant syndrome fibrodysplasia ossificans progressiva (FOP), although there is no cancer predisposition in FOP.
Receptor tyrosine kinase amplification: PDGFRA amplification occurs in approximately 30% of cases, with lower rates of amplification observed for some other receptor tyrosine kinases (e.g., MET and IGF1R).
TP53 deletion: DIPG tumors commonly show deletion of the TP53 gene on chromosome 17p. Additionally, TP53 is commonly mutated in DIPG tumors, particularly those with histone H3 gene mutations. Aneuploidy is commonly observed in cases with TP53 mutations.
The gene expression profile of DIPG differs from that of non–brain stem pediatric high-grade gliomas, further supporting a distinctive biology for this subset of pediatric gliomas.
DIPG Signs and symptoms
The symptoms are related to the internal pressure that the tumour applies on the brain stem. Occasionally they can cause increased pressure in the head (raised intracranial pressure). Rarely they spread into the spine. Symptoms include:
- Swallowing problems
- Slurred speech
- Facial Weakness
- Abnormal Gait (the way the child walks)
- Difficulty with tasks like handwriting
- Gradual decline in school work
- Changes in personality and behaviour
If there is increased pressure in the head:
- Nausea and Vomiting
If the tumour spreads to the spine:
- Back pain
- Difficulty walking
- Problems with bowel and bladder control
Tests / investigations
Some tests will need to be carried out to find out as much as possible about the type, position and size of the tumour. This will help us to decide on the best treatment for your child. These tests include:
CT Scan – it is likely a CT scan of your child’s brain was the first specific test carried out at your local hospital. Although MRI scans are usually the best way of seeing the tumour and the effects of treatment, sometimes CT scans are also useful.
MRI Scan – this scan allows us to see the brain and spine in great detail and is used regularly to diagnose and follow the effect treatment is having on your child’s tumour.