Semel Institute for Neuroscience and Human Behavior, David Geffen School of Medicine at UCLA, Los Angeles, CA, 90095, USA.
Department of Psychiatry and Biobehavioral Research, David Geffen School of Medicine at UCLA, Los Angeles, CA, 90095, USA.
J Neurooncol. 2017 Sep;134(3):505-512. doi: 10.1007/s11060-017-2379-y. Epub 2017 Feb 23.
Gliomas are the most malignant and aggressive form of brain tumors, and account for the majority of brain cancer related deaths. Malignant gliomas, including glioblastoma are treated with radiation and temozolomide, with only a minor benefit in survival time. A number of advances have been made in understanding glioma biology, including the discovery of cancer stem cells, termed glioma stem cells (GSC). Some of these advances include the delineation of molecular heterogeneity both between tumors from different patients as well as within tumors from the same patient. Such research highlights the importance of identifying and validating molecular markers in glioma. This review, intended as a practical resource for both clinical and basic investigators, summarizes some of the more well-known molecular markers (MGMT, 1p/19q, IDH, EGFR, p53, PI3K, Rb, and RAF), discusses how they are identified, and what, if any, clinical relevance they may have, in addition to discussing some of the specific biology for these markers. Additionally, we discuss identification methods for studying putative GSC's (CD133, CD15, A2B5, nestin, ALDH1, proteasome activity, ABC transporters, and label-retention). While much research has been done on these markers, there is still a significant amount that we do not yet understand, which may account for some conflicting reports in the literature. Furthermore, it is unlikely that the investigator will be able to utilize one single marker to prospectively identify and isolate GSC from all, or possibly, any gliomas.
神经胶质瘤是最恶性和侵袭性的脑肿瘤,占大多数与脑癌相关的死亡病例。恶性神经胶质瘤,包括胶质母细胞瘤,采用放疗和替莫唑胺治疗,仅在生存时间上略有改善。在了解神经胶质瘤生物学方面已经取得了一些进展,包括癌症干细胞的发现,称为神经胶质瘤干细胞(GSC)。这些进展中的一些包括在不同患者的肿瘤之间以及同一患者的肿瘤内,对分子异质性进行了描绘。此类研究强调了识别和验证神经胶质瘤分子标志物的重要性。本篇综述旨在为临床和基础研究人员提供实用资源,总结了一些更为知名的分子标志物(MGMT、1p/19q、IDH、EGFR、p53、PI3K、RB 和 RAF),讨论了它们的识别方法,以及它们可能具有哪些临床相关性,此外还讨论了这些标志物的特定生物学特性。此外,我们还讨论了研究假定的 GSC(CD133、CD15、A2B5、巢蛋白、ALDH1、蛋白酶体活性、ABC 转运蛋白和标记保留)的鉴定方法。虽然对这些标志物进行了大量研究,但仍有许多我们尚未了解的内容,这可能解释了文献中存在一些相互矛盾的报告。此外,研究人员不太可能能够利用单一标志物来前瞻性地识别和分离所有或可能的任何神经胶质瘤中的 GSC。