New study identifies first gene associated with familial glioma

An international consortium of researchers led by Baylor College of Medicine has identified for the first time a gene associated with familial glioma (brain tumors that appear in two or more members of the same family), providing new support that certain people may be genetically predisposed to the disease. The findings appear in the Journal of the National Cancer Institute.

The study recruited 435 families in which glioma occurred from 14 centers in the United States, Sweden, Denmark, the United Kingdom, and Israel. The team applied a method of genetic testing called whole exome sequencing (which determines the DNA sequence of the exons, or protein-coding regions, of tens of thousands of genes simultaneously) on 90 individuals with glioma from 55 families enrolled in the project.

The data identified mutations in a gene called POT1, which was present in two of the families. In one family, six members harbored a mutation of POT1 that is rarely seen in other populations, and among them three developed glioma. In another family, six individuals carried a different mutation in the POT1 gene and two developed glioma.

The mutations in the POT1 gene are predicted to result in a disruption in a region of the POT1 protein that is important for its function at telomeres, the protective caps at the end of chromosomes. Although short telomeres have been implicated in a wide range of cancers, longer telomeres have previously been associated with some cancers as well, researchers note.

“As we learn more about POT1 and familial glioma, it may help us in counseling families about glioma risk or possibly point the way to new therapeutic targets,” says Dr. Sharon Plon, PhD, a co-author on the study. “This is the beginning of defining the genes for familial glioma.”