EPCO-08. CONSERVED FEATURES OF TERT PROMOTER DUPLICATIONS REVEAL AN ACTIVATION MECHANISM THAT MIMICS HOTSPOT MUTATIONS IN CANCER

Abstract Mutations in the TERT promoter are single most common non-coding mutation cancer and represent genetic underpinnings of tumor cell immortality. Beyond two point mutations, G228A G250A, which selectively recruit ETS factor GABP to activate TERT, significance other variants unknown. We identified duplications wildtype sequence within core region 7 different types that have strikingly similar features including size, insertion position, inclusion one native motifs. Each duplication activates a level as G250A is critically dependent on site. The tetramer binds duplicated by virtue motif its version with precise spacing, it necessary for transcriptional activation all tested. Spatiotemporal analysis multifocal glioblastoma shows clonal readily detectable at bulk tissue. conclude recurrent functionally mechanistically equivalent hotspot mutations confer shared mechanism these divergent somatic alterations suggests strong selective pressure recruitment TERT.