News Story

Researchers Identify New Genetic Risk Factor for NF1-Associated Glioma

A new study, spearheaded by Dr. Joshua Rubin and his colleagues, found that subtle changes in the genes of children with NF1 may increase their risk of developing a brain tumor (glioma). Using a combination of Nf1 genetically-engineered mice and NF1 patient DNA samples, they found that slight changes, termed genetic polymorphisms, in the ADCY8 gene, altered the likelihood of glioma formation in children with NF1.
In this report, this investigative team discovered that these genetic polymorphisms increased the risk of glioma in girls, while decreasing the risk in boys. The ADCY8 gene controls cyclic AMP levels in the brain, which are important for cell survival. Importantly, using Nf1 genetically-engineered mice developed in the laboratory of Dr. David Gutmann, they found that sex differences exist in cyclic AMP regulation. Previous studies from Dr. Rubin’s laboratory had shown that cyclic AMP is one of the key molecules important for Nf1 optic glioma growth in mice.
These exciting findings could help support personalized approaches to risk assessment, advance our understanding of the factors that favor glioma formation, and potentially identify new treatments for these common brain tumors in children with NF1.
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Warrington NM, Sun T, Luo J, McKinstry RC, Parkin PC, Ganzhorn S, Spoljaric D, Albers AC, Merkelson A, Stewart DR, Stevenson DA, Viskochil D, Druley TE, Forys JT, Reilly KM, Fisher MJ, Tabori U, Allen JC, Schiffman JD, Gutmann DH, Rubin JB. The cyclic AMP pathway is a sex-specific modifier of glioma risk in type 1 neurofibromatosis patients. Cancer Res. 75(1): 16-2, 2015.