What is the Difference Between DIPG and DMG and what is the H3K27 Histone Mutation? | The Cure Starts Now What is the Difference Between DIPG and DMG and what is the H3K27 Histone Mutation? | The Cure Starts Now thecurestartsnow.org


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What is the Difference Between DIPG and DMG and what is the H3K27 Histone Mutation?

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The following article originally appeared on DIPG.org

DIPG (Diffuse Intrinsic Pontine Glioma) and DMG (Diffuse Midline Glioma) are often categorized together but can have different treatments that can lead to slightly different prognosis paths. Still, much of the science, the research, foundational funding and data for both types of brain tumors are grouped under DIPG, mainly because historically much of the work researching DIPG since around 2012 led to the reclassification and current definitions of DMG.

DIPG is a type of brain tumor found in an area of the brainstem known as the pons. The name diffuse intrinsic pontine glioma describes how the tumor grows, where it is found, and what kinds of cells give rise to the tumor. Diagnoses of DIPG are typically made through an MRI or radiological exam.  Diffuse means that the tumor is not well-contained – it grows out into other tissue so that cancer cells mix with healthy cells. Intrinsic simply means "in", referring to the point or origin. Pontine indicates that the tumor is found in a part of the brainstem called the pons. The pons is responsible for a number of important bodily functions, like breathing, sleeping, bladder control, and balance.  Glioma is a general term for tumors originating from glial cells. Glial cells are found throughout the brain. They make up the white matter of the brain that surrounds and supports the neurons (neurons are cells that carry messages in the brain).  The lowest grade consistent with a DIPG is a grade 2 tumor, but many DIPG tumors will be grade 3 or 4 (the most-aggressive, fastest-growing grades).

Certain factors may lead to improved survival prognosis with those diagnosed with DIPG. They include those patients diagnosed before the age of 3 or after the age of 10, those patients with few symptoms prior to diagnosis and those patients with limited to no growth beyond the pons.

Ultimately some DIPG tumors reviewed by MRI may be termed as “atypical” possibly leading to other diagnosis methodologies such as a biopsy to determine if other treatment options exist.  For this reason it is strongly recommended that patients diagnosed with DIPG seek enrollment in the International DIPG/DMG Registry or the SIOPe DIPG Registry so that the MRI may be centrally reviewed by radiologists with strong experience with these types of tumors.

DMG, on the other hand, is a clarified diagnosis of a DIPG through a biopsy and more recently through blood biopsy methods.  An astrocytoma located along the midline of the brain, it can also be found in midline structures like the spinal cord or thalamus.  Often these tumors start as “atypical” DIPG and are formally diagnosed as DMG.  Still aggressive, they are often classified as a grade 4 tumor and tend to spread to neighboring tissue. 

Starting as early as 2012, due to the surgical advancement of biopsy methods, it was discovered that DMGs also have a specific mutation in the H3F3A gene and are commonly referred to as H3K27 mutant.  As these have received genomic analysis through leading registries such as the International DIPG/DMG Registry and the SIOPe DIPG Registry, genetic marker identification has led to the discovery of certain drugs and treatments that may be applicable.  This has also led to the findings reported in 2018 in the Journal of Clinical Oncology (https://thecurestartsnow.org/impact/news/characteristics-of-long-term-survivors-of-dipg/) detailing a slightly higher chance of improved prognosis with those patients that present the H3K27 mutation.

While a World Health Organization reclassification of these astrocytomas categorizes DIPG as a subgroup of DMG, most researchers and foundations tend to regard DMGs as a parallel group to DIPG in that the diagnosis of a patient starts with DIPG and then is later identified as a DMG after biopsy or blood biopsy methods.

Learn more about the diagnosis and imaging of DIPG