mutation is the earliest genetic alteration in low-grade gliomas (LGGs), but its role in tumor recurrence is unclear. Mutant IDH1 drives overproduction of the oncometabolite d-2-hydroxyglutarate (2HG) and a CpG island (CGI) hypermethylation phenotype (G-CIMP). To investigate the role of mutant IDH1 at recurrence, we performed a longitudinal analysis of 50 mutant LGGs. We discovered six cases with copy number alterations (CNAs) at the locus at recurrence. Deletion or amplification of was followed by clonal expansion and recurrence at a higher grade. Successful cultures derived from mutant, but not wild type, gliomas systematically deleted in vitro and in vivo, further suggestive of selection against the heterozygous mutant state as tumors progress. Tumors and cultures with CNA had decreased 2HG, maintenance of G-CIMP, and DNA methylation reprogramming outside CGI. Thus, while mutation initiates gliomagenesis, in some patients mutant IDH1 and 2HG are not required for later clonal expansions.