Acquired genetic and cell-state changes in IDH-mutant glioma progression

Human glioma samples Frozen glioma tissue specimens with the IDH1 or IDH2 mutation were collected with informed consent from the following tissue source sites: Saint Joseph’s Hospital, the Luxembourg Institute of Health-NORLUX (LIH-NORLUX), the MD Anderson Cancer Center (MDACC), Seoul National University (SNU) Hospital and the Pitié-Salpêtrière Hospital. Sample collection was approved by each tissue source site’s Institutional Review Board (IRB). The IRB protocol numbers of respective institutes are as follows; MDACC, 2012-0441; LIH-NORLUX, 201201/06; SNU, H-2004-049-1116; Pitié-Salpêtrière Hospital, 96-900; and Saint Joseph’s Hospital, 2020-NHSR-0084. IDH mutation status and chromosome 1p and 19q co-deletion status were obtained from pathology reports and confirmed by DNA-seq in this study when available. Detailed clinical information, including patient sex, age at diagnosis and treatment information, is provided in Supplementary Table 1 . Astrocytoma samples with evidence of CDKN2A homozygous deletion were assigned grade 4 status in accordance with the 2021 WHO diagnostic criteria 1 . Adjacent fragments from each glioma sample were aliquoted for single-nucleus assays and bulk tissue nucleic acid isolation when sufficient material was available. Tissue processing and nucleus isolation Isolation of nuclei from frozen glioma samples was performed by three separate laboratories using two different protocols. …