Five genes hold key to meningioma make up

By Helen Albert, Senior medwireNews Reporter

medwireNews: Research published in Science shows that mutations in five genes characterize most meningiomas.

The team, led by Murat Günel (Yale School of Medicine, New Haven, Connecticut, USA), hopes the discovery will help scientists develop personalized treatments for this mostly benign (90% of cases), but common brain tumor.

Previous research demonstrated that a loss of function mutation in the neurofibromin 2 gene (NF2) accounts for 40-60% of all meningioma tumors, but the genetic background of the remaining tumors was less clear.

Günel and colleagues discovered four additional genes associated with meningioma following genome-wide genotyping and exome sequencing of 50 non-irradiated grade I and II meningiomas.

As well as mutations in NF2, the team found that the genes tumor necrosis factor receptor-associated factor 7 (TRAF7), Krupple-like factor 4 (KLF4), v-akt murine thymoma viral oncogene homolog 1 (AKT1), and Smoothened, frizzled family receptor (SMO) had a higher number of somatic mutations than would be expected by chance.

An additional analysis of 250 non-irradiated meningiomas plus the original 50 tumors, focusing on NF2, TRAF7, KLF4, AKT1, and SMO, showed that all 300 meningiomas had mutations in at least one of the five genes.

Overall, NF2 mutations were seen in 36.0% of the tumors, TRAF7 mutations (always exclusive of NF2 mutations) in 24.0%, KLF4 mutations in 10.3% (always co-occurring with TRAF7 mutations), AKT1 mutations in 12.7% (co-occurring with TRAF7 mutations in 25 of 38 tumors), and SMO mutations in 3.7% (occurring alone in eight of 11 tumors).

The researchers note that the tumors with TRAF7 mutations, a gene not previously associated with cancer, occur mostly in the skull base and are largely benign, whereas those with NF2 mutations are more likely to become malignant.

"Combining knowledge of these mutations with the location of tumor growth has direct clinical relevance and opens the door for personalized therapies," said Günel in a press statement.

Indeed, mutations in SMO and AKT1 have already been linked with other cancers, and mutations in SMO are the target for an approved drug for basal cell carcinoma.

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