Several types of very aggressive and fatal pediatric brain tumors appear during brain development, found oncologists associated with the Research Institute of the McGill University Health Center (RI-MUHC).
In fact, Dr. Claudia Kleinman and her colleagues have shown that some brain tumors in children are caused by stopping the development of embryonic cells.
Thus, they established that the genetic event that triggers the disease occurs in the earliest stages of cellular development, often in prenatal phases, and long before a woman knows she is pregnant.
We have determined that stopping cellular development in the bridge and in the forebrain, from which some of these aggressive pediatric tumors originate, is responsible for several childhood brain cancers.
Rather than continuing normally, cell development is halted and they turn into malignant tumors, but they retain many of the characteristics of the original cells
, says Dr. Kleinman.
The Montreal team was able to determine the origin of the tumors among the hundreds of different types of cells present in the brain.
Landmarks
- Brain tumors are the leading cause of cancer-related deaths in children;
- There is no effective treatment for many of these tumors;
- Survival is often less than two years.
It is thanks to the new technologies that make it possible to analyze the tumor cells one by one that the researchers have been able to establish that a stop of the development would be at the origin of several infantile cancers.
We are talking about Peter Pan syndrome because these cells are stuck in time, unable to age, and that is why these tumors develop.
The next step
Scientists must now find a way to unlock
these cells to help differentiate them and allow normal processes to take over
.
Once we understand the underlying mechanisms, we can begin to look for how to unlock cell development. The complexity of the brain is staggering and we have now targeted where to look.
Better understand the normal development
Using single-cell sequencing techniques now available and large-scale data analysis, the researchers have succeeded in creating the first complete profile of the normal prenatal bridge, an important structure located on the upper brain stem that controls the breathing, as well as sensations like hearing, taste and balance.
Scientists have determined the molecular identity of the types of cells present in this bridge and in other brain regions, as well as the dynamics of their differentiation.
They created an atlas of more than 65,000 individual cells and 191 distinct cell populations. They then integrated this atlas with patient samples and discovered the origins of several tumors, including:
- WNT medulloblastomas
- Embryonic tumors with multilayer rosettes (ETMR)
- High grade gliomas (GHG).
The results of this work support the existence of a common cause for these tumors, where genetic modifications in certain vulnerable cell types disrupt developmental gene expression programs, ultimately leading to the development of cancer.
The genesis of tumors is very early in brain development, which means that there is really no trigger in the environment or preventative measures that parents can take.
The research team now wants to deepen their understanding of these tumors in order to one day stop their progression.
The details of this work are published in the journal Nature Genetics.
