CDKN2A deletion associated with poor prognosis in patients with TERT promoter wild-type, IDH wild-type glioblastoma

Background The most common alterations in IDH wild-type primary glioblastoma (GBM) are mutations in the promoter region of the telomerase reverse transcriptase gene ( TERT p). This retrospective study investigated whether the impact of clinicopathological factors on prognosis in patients with GBM depends on TERT p status. Methods Among 112 cases of IDH wild-type GBM, 70 patients (62.5%) had the TERT p mutation. Clinical, immunohistochemical, and genetic factors (ATRX expression, and O 6 -methylguanine-DNA methyltransferase promoter [ MGMT p] methylation), and copy number alterations (CNAs) were investigated. Results Loss of ATRX, PDGFR amplification/gain, MDM2 amplification/gain, and TP53 hemizygous deletion were more frequent in patients with TERT p wild-type GBM ( P = 0.005, P = 0.009, P = 0.033, P = 0.009, respectively). EGFR amplification/gain and PTEN deletion were more frequent in those with TERT p mutant GBM (both P < 0.001). Postoperative residual tumor volume and MGMT p methylation were significantly correlated with PFS and OS in patients with TERT p mutant GBM. Only CDKN2A deletion was strongly correlated with poor OS in patients with TERT p wild-type GBM ( P < 0.001). Conclusions CDKN2A deletion alone was associated with the prognosis of TERT p wild-type GBM. Therefore, TERT p wild-type GBM may be a distinct clinical subtype of IDH wild-type GBM.