Supplementary Material for: IDH-mutant WHO Grade 4 Astrocytoma with BCOR Alteration

BCOR, a transcriptional regulator, has been increasingly recognized for its involvement in various human cancers, where it plays a significant role in neoplastic transformation and tumor progression. As a component of the noncanonical polycomb repressive complex 1 (PRC1), BCOR contributes to transcriptional repression through histone modifications. BCOR alterations have been also identified in some brain tumors, with mutations such as nonsense, frameshift, and splice site alterations reported in glial tumors, astroblastomas, pineoblastomas, and medulloblastomas. While BCOR alterations have not previously been reported in IDH-mutant WHO grade 4 astrocytoma, we describe a rare case involving an adult patient who presented with a recurrent, contrast-enhancing tumor in the left parietal region. Following complete surgical resection, the biopsy confirmed an IDH-mutant WHO grade 4 astrocytoma. Next-generation sequencing (NGS) using the TruSight Oncology 500 (TSO500) platform, which included both DNA and RNA sequencing, revealed mutations in IDH1, ATRX, and EGFR, alongside a novel BCOR internal tandem duplication (ITD). This discovery highlights a unique finding of BCOR alteration in an IDH-mutant WHO grade 4 astrocytoma. The presence of a BCOR ITD in this context expands the molecular spectrum of high-grade astrocytomas and suggests the need for further investigation into its potential implications for tumor behavior, prognosis, and therapeutic targeting.

BCOR作为转录调节因子，目前已被广泛认识到参与各类人类癌症的发生发展，在肿瘤转化与肿瘤进展中发挥关键作用。作为非经典多梳蛋白抑制复合体1（PRC1）的组成部分，BCOR可通过组蛋白修饰介导转录抑制。此前已在部分脑肿瘤中检出BCOR基因改变，包括在神经胶质瘤、星形母细胞瘤、松果体母细胞瘤及髓母细胞瘤中报道的无义突变、移码突变与剪接位点变异。尽管此前尚无BCOR基因改变出现在异柠檬酸脱氢酶（isocitrate dehydrogenase, IDH）突变型WHO 4级星形细胞瘤中的相关报道，本研究报道了一例罕见病例：一名成年患者左侧顶叶出现复发性强化肿瘤。经完全手术切除后，活检证实为IDH突变型WHO 4级星形细胞瘤。采用包含DNA与RNA测序的TruSight肿瘤500（TruSight Oncology 500, TSO500）平台进行二代测序（next-generation sequencing, NGS），结果检出IDH1、ATRX及EGFR基因突变，同时发现一种新型BCOR内部串联重复（internal tandem duplication, ITD）。该发现揭示了IDH突变型WHO 4级星形细胞瘤中存在BCOR基因改变这一独特现象，此病例中检出的BCOR ITD拓展了高级别星形细胞瘤的分子谱范围，同时提示需进一步研究其对肿瘤生物学行为、预后及治疗靶点选择的潜在影响。