New Insights into Genetic Variations Influencing Childhood Brain Tumors

Recent research has shed light on the genetic factors that contribute to the development of childhood brain tumors. Scientists from Baylor College of Medicine and other collaborating institutions investigated the connection between large-scale genetic variations, known as germline structural variations (SVs), and epigenetic modifications like DNA methylation. This study is groundbreaking because it explores how inherited structural differences in DNA can influence gene activity in tumors, beyond the traditional focus on small mutations.

Germline SVs involve significant alterations in DNA segments, such as deletions, duplications, or rearrangements, which can impact gene regulation when occurring near critical control regions of the genome. DNA methylation, another key factor in gene regulation, involves adding chemical tags to DNA, which can turn genes on or off without changing the underlying genetic sequence. Both these mechanisms are associated with cancer but were previously studied separately.

The research analyzed 1,292 pediatric brain tumor samples provided by the Children's Brain Tumor Network. The findings revealed that thousands of SVs are linked to changes in DNA methylation patterns in tumors. These alterations often affected gene enhancer regions, which are pivotal in controlling gene expression. Notably, several affected genes are known to play roles in cancer predisposition and patient survival, including genes like MSH2, RSPA, PALB2, and POLD4.

According to Dr. Chad Creighton, co-author of the study, understanding how larger genetic variations influence gene expression offers a different perspective on cancer development. This research emphasizes that structural variations can have profound effects on gene activity, especially when they occur near essential regulatory elements.

The significance of these findings lies in their potential to improve early detection and personalized treatment strategies for children at risk of brain tumors. By mapping the genetic and epigenetic landscape, scientists hope to develop better tools for risk assessment and targeted therapies.

The full study titled "Global DNA methylation differences involving germline structural variation impact gene expression in pediatric brain tumors" is published in Nature Communications (2025). More details can be found here. This research was supported by Baylor College of Medicine and aims to deepen our understanding of genetic and epigenetic factors in childhood cancer.

Source: https://medicalxpress.com/news/2025-05-uncovers-source-genetic-variation-childhood.html