New Study Identifies First Gene Associated With Familial Glioma

New Study Identifies First Gene Associated With Familial Glioma
Hypothalamic Glioma  (Image source)
Researchers have for the first time identified a gene associated with familial glioma, a type of brain tumor 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 are published in Journal of the National Cancer Institute.
It is widely thought amongst the clinical community that there is no association between family history and development of glioma. Because very little is known about the contributing genetic factors, when cases occur in two or more family members, it is viewed as coincidental. However, the researchers of the current study estimates that approximately five percent of brain tumors run in families.
The team applied an advanced 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. They combed through the sequencing data and 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.
They further validated the finding in a separate group of individuals and families with glioma in which they identified an additional mutation in POT1 in one family.
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.
POT1 modulates the activity of telomerase, a highly regulated enzyme that lengthens telomeres. This is a very important process, and when the process is disrupted with a mutation in a gene like POT1, the telomeres elongate.
POT1 also has recently been observed in familial melanoma in association with longer telomeres by another research team, which is not surprising to the scientists, as they have previously reported a higher incidence of melanoma in first degree relatives of glioma patients.  
While the researchers suspect there could be a number of other genes associated with familial glioma, this is the beginning of defining the genes for the disease. More information about familial glioma and POT1 can help counsel families about glioma risk, and possibly point the way to new therapeutic targets.