DIPG (Diffuse Intrinsic Pontine Glioma) and DMG (Diffuse Midline Glioma)

What is the Condition?

• Pediatric diffuse intrinsic pontine gliomas (DIPGs)/ diffuse midline glioma (DMG) are brain tumors that are diagnosed in children (peak incidence 5-9 years old). They make up around 10% of all pediatric brain tumors.

• DIPGs are found in the pons (the middle portion of the brainstem), and, grow throughout (“infiltrate”) the pons, taking up at least half of this important structure. They can grow into other area of the brainstem, and grow into the CSF-filled fourth ventricle next to the pons.

• “DIPG” is a diagnosis that is given based on the radiology (MRI) results alone. If the DIPG is biopsied - a diagnosis based on the pathology is also given. Most DIPGs (70-90%) that are biopsied have the pathology diagnosis of “diffuse midline glioma”, which is a term used for higher grade glioma (grade II-IV) in a midline brain structue, including the thalamus, brainstem or spinal cord (i.e. “DIPG” is a sub-type of “DMG”)

• DMGs are tumors that arise from precursors of astrocytes – supportive cells of the brain named for their star-like shape. They are fast growing tumors and tend to behave aggressively.

• Recent research has shown that 80% of pediatric DMGs are driven by mutations in histone genes H3F3A (H3.3) and HIST1H3B (H3.1), which are proteins scaffolds for DNA. As these mutations have important implications for tumor behavior, treatment, and prognosis, DMGs with a histone mutation are diagnosed as "H3 K27M-mutant diffuse midline glioma."

• Other important genes that are mutated in DMG include the ACVR1 gene, which is involved in developmental regulation, the tumor suppressor gene TP53 (p53), and other genes that result in growth and proliferation of DMG cells, including MYC, PDGFRA and PI3KCA . The molecular features of a DMG may impact tumor prognosis and treatment response. Current investigational therapies are adapted to these molecular features.

What are the Symptoms?

• Headaches, changes in swallowing, vision, or facial movement, and changes in sensation or strength of the arms and legs are the most common early symptoms of DMG/DIPG. Other symptoms may occur depending on the size and location of the tumor.

How is it diagnosed?

• Accurate diagnosis is the single most important factor in creating an effective treatment plan for DMG/DIPG.

• Diagnosis for DMG/DIPG may incorporate:

  • Imaging of the brain (may or may not include spine) with an MRI

  • If diagnosis remains uncertain after imaging or if the patient/family is interested in obtaining additional molecular information from the tumor, biopsy of is performed and the tumor sample is examined to confirm diagnosis

  • Spinal tap, or lumbar puncture, to remove a small sample of cerebrospinal fluid (CSF) to assess for tumor cells, is occasionally performed.

  • Diagnosis and management of DMG/DIPG may benefit from determination of tumor driving mutations in the DNA or RNA of the tumor cells through sequencing performed on tumor tissue

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The University of Michigan Chad Carr Pediatric Brain Tumor Center

HIGH GRADE GLIOMA

What is the Condition?

• Pediatric high-grade gliomas are brain tumors that are diagnosed in children (peak incidence 6-10 years old, but can be found at any age). High grade glioma includes the following subtypes, which are diagnosed and treated similarly: anaplastic astrocytoma (grade III) and glioblastoma (grade IV). High-grade gliomas arising in midline brain structures (brainstem, thalamus, spinal cord) have distinct biology and clinical management and are discussed above (DIPG or DMG).

• High-grade gliomas are tumors that arise from precursors of astrocytes – supportive cells of the brain named for their star-like shape. Using a microscope, pathologists grade gliomas based on features such as their ability to divide and invade normal tissue. High-grade gliomas are faster growing tumors and tend to behave more aggressively than lower grade gliomas. They usually invade locally (only rarely metastasize to other parts of the brain).

• High grade gliomas are usually found in different locations based on the age of the patient (childhood high-grade glioma is usually in the deeper structures such as the thalamus, while adolescent high-grade glioma is often in the more superficial cortex).

• Recent research has shown that pediatric high-grade gliomas are frequently driven by mutations in the DNA of the tumor cells, including the histone gene H3F3A (H3.3), the histone chaperone protein ATRX, the tumor suppressor gene TP53 (p53), and genes involved in cell growth and proliferation, including CDK4/6, and PDGFRA . The molecular features of a high-grade glioma may impact tumor prognosis and treatment response. Current investigational therapies are adapted to these molecular features.

Read more on the

The University of Michigan Chad Carr Pediatric Brain Tumor Center