Chemotherapy may soon be able to replace surgery as a safer and cheaper treatment for the most common type of brain tumor.
A Yale study published Jan. 24 in the journal Science revealed that mutations in just five genes are responsible for the majority of these tumors, called meningiomas. Before the study, only one gene, called NF2, had been linked with meningiomas, but NF2 mutations accounted for only 36 percent of tumors in this study. By understanding the roles of these new genes, scientists may be able to develop drugs to cure patients with meningiomas.
“This is the first time we’ve found these new genes that are causing meningiomas,” said lead author Victoria Clark GRD ’15, M.D./Ph.D. student at the Medical School. “Chemotherapies that target these new pathways could offer a better treatment option than brain surgery.”
The researchers sequenced the coding part of the genomes of 50 meningiomas and discovered that 90 percent of them showed associations with the NF2 gene and four additional genes — two of which have never before been linked to cancer. The team then analyzed 250 more tumors for those five genes, and found mutations in almost 80 percent of them. Clark said the remaining 20 percent of tumors still needs to be accounted for genetically, adding that an even larger sample size may have revealed other genes responsible for meningiomas. The study confirmed the findings of a Harvard study published Jan. 20 in Nature that had discovered the role of two of the genes in meningioma development.
When the meningiomas were categorized by the mutant gene, researchers found that tumors in certain parts of the brain were much more likely to have one type of mutation than others. This genetic map could help doctors identify a meningioma’s cause by its location in the brain, and deliver the appropriate form of chemotherapy, Clark said. Certain mutations are more common in specific parts of the brain than others, so understanding the distribution of these mutations will help doctors determine the gene responsible for a specific case of meningioma and prescribe a suitable treatment, she added.
“It’s early to say whether any specific therapeutic options are useful for treating meningiomas,” said study senior author Rameen Beroukhi, assistant professor at Harvard Medical School.
Chemotherapeutic drugs have already been developed to combat two mutations associated with meningiomas, Beroukhi said. One drug has already been approved by the Food and Drug Administration, and the other is undergoing clinical trials. However, researchers have only begun to characterize the two other mutations discovered by the study, and Clark said her next steps will be to conduct a more thorough analysis of how these mutations lead to meningiomas.
Each year, 6,500 people are diagnosed with meningiomas in the United States.