3D DNA Organization Influences the Progression of Aggressive Brain Tumors, Study Reveals

Glioblastoma (GBM) is the most common type of cancerous brain tumor in adults, accounting for 50.1% of all primary malignant cases. According to the National Brain Tumor Society (NBTS), more than 14,490 Americans are expected to get diagnosed with GBM in 2023.

In Sweden, a team of researchers has made a discovery that paves the way for new treatments for brain tumors.

What is Glioblastoma?

Glioblastoma is a type of cancer that starts as a growth of cells in the brain or spinal cord. It forms from cells called astrocytes, which support nerve cells. This aggressive brain tumor can invade and destroy healthy tissues as it grows quickly.

GBMs are highly varied tumors that contain different types of "glial" brain cells. Cell types within these tumors are variably specialized and can closely interact with normal brain cells and cells of the blood vessels.

People who develop glioblastoma develop symptoms rapidly because of the mass effect of the tumor or from the fluid that surrounds the tumor. The common presenting symptoms at diagnosis include severe headache, seizures, memory and language problems, and muscle weakness or paralysis.

Impact of DNA Organization

At Umeå University, a pioneering study was conducted by researchers, which allowed them to identify the most critical factors behind the response of tumors to nerve cells. They discovered that the 3D organization of DNA influences the progression of glioblastoma.

One possible way to understand the aggressive form of brain tumor is through DNA analysis. It has been accepted that changes in parts of DNA that do not contain genes can increase the risk of cancer and affect the function of genes. DNA contains so-called enhancers, or "switches," which ensure that the right genes are activated in the suitable cells at the right time.

Strictly controlling the genes is very crucial. If errors occur in these "switches," or abnormalities emerge in the way they contact the genes, then there could be changes in gene expression, eventually leading to cancer.

The Swedish researchers made a step forward by discovering the synaptic connections between nerve cells and brain tumors. Nerve cells send electrical signals to brain tumor cells, which make them grow and spread.

Led by Umeå University assistant professor Silvia Remeseiro, the scientists used cells from glioblastoma patients and advanced techniques to analyze the structure and epigenetics of DNA. From the result of the analysis, the researchers identified the key elements that are crucial to this neuron-to-tumor communication.

These agents are named SMAD3 and PITX1. They are proteins that bind to and control the DNA switches which regulate gene expression. In experiments involving cell cultures and mice, the researcher saw how SMAD3 inhibition, together with the signals from the nerve cells, allowed the tumor to grow and spread.

Alterations in DNA structure and enhancers affect the expression of genes. This study highlights that these alterations are crucial for the communication between neurons and tumor cells. It also offers insights into how glioblastoma cells become more dangerous in response to the signals from the nerve cells.