Molecular analysis of a gliosarcoma with distinct oligodendroglioma and sarcomatous components ("Oligosarcoma").

Here, we report a rare case of a 59-year-old woman with a TERT promoter-wildtype oligosarcoma developed after resection of an IDH-mutant oligodendroglioma with1p/19q codeletion followed by maintenance temozolomide therapy. The oligosarcoma exhibited distinct oligodendroglioma and sarcomatous components, both of which were diffusely positive for IDH1 R132H and showed strong, diffuse nuclear accumulation of p53. Molecular analyses were performed separately for each component using fluorescence in situ hybridization, Sanger sequencing, amplicon-based next generation sequencing, and DNA methylation profiling. The results indicated that the clones observed in oligodendroglial and sarcomatous components originated from a common precursor harboring IDH1 p.R132H, TP53 p.P250L, and PIK3CA p.C90G mutations together with 1p/19q codeletion, and subsequently acquired additional mutations and chromosomal abnormalities through subclonal evolution and biphenotypic differentiation. Specifically, the oligodendroglial component acquired a KRAS p.G12D mutation and polysomy of chromosome 1q and 19p, whereas the sarcomatous component harbored PTEN p.G165R and PTEN p.Q171* mutations and copy-number neutral loss of heterozygosity of 1p. No TERT promoter mutation was detected. DNA methylation profiling classified the gliomatous component of the oligosarcoma as “oligosarcoma, IDH-mutant” with a calibrated score of >0.99.