PDTM-33. ATRX LOSS CONFERS ENHANCED SENSITIVITY TO COMBINED PARP INHIBITION AND RADIOTHERAPY IN PAEDIATRIC GLIOBLASTOMA MODELS

ABSTRACT: Abstract Paediatric high grade glioma (pHGG) are defined by recurrent mutations in H3 histones, as well as frequent alterations in the SWI/SNF chromatin remodelling gene ATRX (α-thalassemia mental retardation X-linked), although the precise role of ATRX in tumorigenesis remains unclear. We sought to explore this using genomic analysis of patient samples, CRISPR-Cas9 engineered isogenic ATRX knockout (KO) cell lines and primary-patient-derived cultures. In combined retrospective and prospective cohorts of pHGG samples, we found ATRX mutations in 95/510 (18.6%) cases (27% hemispheric glioblastoma, 13% diffuse midline glioma), with the majority of truncating mutations found in the ADD domain, and missense mutations almost exclusively in the helicase domain. ATRX mutations commonly co-segregat

SUBMITTER: Fazal Salom J 

PROVIDER: S-EPMC6217705 | biostudies-literature | 2018 Nov

REPOSITORIES: biostudies-literature