Identification of Meningioma Mutant Genes May Lead to Drug Treatment

Cancer researchers have identified two mutations that characterize about 15% of meningiomas and may be targets for drugs designed to kill this slow growing, but potentially fatal form of brain cancer.

Investigators at the Dana-Farber Cancer Institute (Boston, MA, USA) performed whole-genome or whole-exome (protein-coding regions) sequencing on 17 meningiomas that had been removed from patients and focused sequencing on an additional 48 tumors to identify and validate somatic genetic alterations.

They reported in the January 20, 2013, online edition of the journal Nature Genetics that most meningiomas had simple genomes, with fewer mutations, rearrangements, and copy-number alterations than reported in other tumors in adults. However, several meningiomas harbored more complex patterns of copy-number changes and rearrangements. The tumor suppressor gene NF2 (neurofibromatosis type-2) was inactivated in 43% of tumors, and alterations in epigenetic modifiers were present in an additional 8% of tumors.

A major finding was that a subset of meningiomas lacking NF2 alterations harbored recurrent oncogenic mutations in the genes AKT1 (v-akt murine thymoma viral oncogene homolog 1) and SMO (smoothened, frizzled family receptor) and exhibited immunohistochemical evidence of activation of these pathways. Mutated AKT1, which is a component of the PI3K-AKT-mTOR pathway that has been implicated in breast, colorectal, and lung cancers, was discovered in five tumors. Mutated SMO, which is a member of the Hedgehog pathway, was found in three tumors.

“Clinically, there is no medical treatment for meningioma that is known to be effective,” said senior author Dr. Rameen Beroukhim, assistant professor of medicine at the Dana-Farber Cancer Institute. “The discovery of the mutations in some meningiomas is potentially the first path to an effective medical treatment. The wonderful thing about those mutations is that there are already drugs in the clinic to target cancers with those mutations.”

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Dana-Farber Cancer Institute