Glioblastoma (GBM), the most malignant of primary brain tumors, is a devastating and deadly disease, with a median survival of 14 months from diagnosis, despite standard regimens of radical brain tumor surgery, maximal safe radiation, and concomitant chemotherapy. GBM tumors nearly always re-emerge after initial treatment and frequently display resistance to current treatments. One theory that may explain GBM re-emergence is the existence of glioma stemlike cells (GSCs). We sought to identify variant protein features expressed in low passage GSCs derived from patient tumors. To this end, we developed a proteomic database that reflected variant and nonvariant sequences in the human proteome, and applied a novel retrograde proteomic workflow, to identify and validate the expression of 126 protein variants in 33 glioma stem cell strains. These newly identified proteins may harbor a subset of novel protein targets for future development of GBM therapy.

中文翻译：

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胶质瘤干细胞中的变异蛋白的大规模鉴定

胶质母细胞瘤（GBM）是原发性脑肿瘤中最恶性的一种疾病，具有毁灭性和致命性，尽管采取了根治性脑肿瘤手术，最大的安全放疗和伴随化疗的常规方案，但从诊断开始的中位生存期为14个月。GBM肿瘤在初始治疗后几乎总是重新出现，并经常表现出对当前治疗的抵抗力。可以解释GBM重新出现的一种理论是神经胶质瘤干样细胞（GSC）的存在。我们试图鉴定在源自患者肿瘤的低代GSC中表达的变异蛋白特征。为此，我们开发了一个蛋白质组学数据库，该数据库反映了人类蛋白质组中的变异和非变异序列，并应用了一种新型的逆行蛋白质组学工作流程，以鉴定和验证126种蛋白质变异在33个神经胶质瘤干细胞株中的表达。