Researchers at Baylor College of Medicine, along with other institutions, have made a significant discovery regarding the genetic factors influencing childhood brain tumors. Their study focused on understanding how gene expression is affected by genetic variations in human cancers. The research team investigated the relationship between two types of genetic variation: germline structural variation (SV) and DNA methylation.
The study, published in Nature Communications, revealed that germline SVs can influence DNA methylation in various brain tumors, which in turn alters the expression of numerous genes. This alteration could play a role in cancer predisposition and patient survival. Dr. Chad Creighton, co-director of cancer bioinformatics at Baylor's Dan L Duncan Comprehensive Cancer Center, explained that they took a novel approach by studying larger genetic code variations rather than individual mutations.
Creighton stated, "Structural variation refers to large differences in the DNA sequence across individuals involving missing, duplicated or switched-around DNA sections." These variations can significantly impact gene regulation when they occur near critical genome control regions.
The researchers analyzed 1,292 samples from children with brain tumors provided by the Children’s Brain Tumor Network (CBTN). They discovered thousands of SVs linked to different levels of DNA methylation in these tumors. Some changes were associated with known cancer predisposition genes such as MSH2, RSPA, and PALB2. Additionally, certain genes like POLD4 were linked to patient survival.
The findings aim to enhance future studies on genetic and epigenetic influences in cancer and may lead to improved diagnostic tools or personalized therapies for children based on their genetic profiles.
Contributors to this research include Fengju Chen, Yiqun Zhang, Wei Li, Fritz J. Sedlazeck, and Lanlan Shen from institutions such as Baylor College of Medicine, University of California – Irvine, and Rice University. The work was supported by a National Institutes of Health grant.
