Optimizing the risk stratification of astrocytic tumors by applying the cIMPACT-NOW Update 3 signature: real-word...

Our work reports implementation of a useful genetic diagnosis for the clinical managment of patients with astrocytic tumors. We investigated 313 prospectively recruited diffuse astrocytic tumours by applying the cIMPACT-NOW Update 3 signature. The cIMPACT-NOW Update 3 (cIMPACT-NOW 3) markers, i.e., alterations of TERT promoter, EGFR, and/or chromosome 7 and 10, characterized 96.4% of IDH^wt cases. Interestingly, it was also found in 48,5% of IDH^mut cases. According to the genomic profile, four genetic subgroups could be distinguished: (1) ID^wt/cIMPACT-NOW 3 (n = 270); (2) IDH^wt/cIMPACT-NOW 3 negative (= 10); (3) IDH^mut/cIMPACT-NOW 3 (n = 16); and 4) IDH^mut/cIMPACT-NOW 3 negative (n = 17). Multivariate analysis confirmed that IDH1/2 mutations confer a favorable prognosis (IDH^wt, HR 2.91 95% CI 1.39-6.06), and validated the prognostic value of the cIMPACT-NOW 3 signature (cIMPACT-NOW 3, HR 2.15 95% CI 1.15-4.03). To accurately identify relevant prognostic categories, overcoming the limitations of histopathology and immunohistochemistry, molecular-cytogenetic analyses must be fully integrated into the diagnostic work-up of astrocytic tumors.