Tine Østergaard presented genomic data from 434 patients with central nervous system (CNS) tumors to investigate the role of the tumor suppressor gene SETD2, which is essential for DNA repair processes. While SETD2 loss has been linked to genomic instability in other cancers, this study found that deleterious SETD2 alterations were relatively rare, detected in only 3% of patients, predominantly in glioblastoma (GBM).

Importantly, SETD2-deficient tumors did not show signs of microsatellite instability or elevated tumor mutational burden (TMB), with a mean TMB of 3.3 mutations/Mb compared to 6.2 mutations/Mb in SETD2-wildtype tumors. These findings suggest that, in primary CNS tumors, SETD2 loss does not confer the same mutational signature observed in other tumor types.

The results provide valuable insight into the molecular landscape of brain tumors and inform future strategies for targeted therapies, including the potential role of ATR inhibitors and immunotherapy in selected patient subgroups.​

Read the abstract here