aService de Neuro-Oncologie, Hôpital Neurologique, Hospices Civils de Lyon bUniversité Pierre et Marie Curie-Paris 6, Centre de Recherche de l'Institut du Cerveau et de la Moelle épinière (CRICM), UMR-S975, Paris cINSERM, U1028; CNRS, UMR5292; Lyon Neuroscience Research Center, Neuro-Oncology and Neuro-Inflammation Team, Université Claude Bernard Lyon 1, Lyon, France.
Curr Opin Oncol. 2013 Nov;25(6):689-94. doi: 10.1097/CCO.0000000000000002.
This review summarizes recent studies on the predictive value of molecular markers in adult gliomas, including 1p/19q codeletion, MGMT methylation, IDH mutation and markers identified using omics and next-generation sequencing studies.
The long-term results of the Radiation Therapy Oncology Group and European Organization for Research and Treatment of Cancer trials in anaplastic oligodendroglial glioma have shown that the 1p/19q codeletion predicts an overall survival benefit from early PCV (procarbazine CCNU vincristine) chemotherapy. This benefit can also be predicted using gene expression-based molecular subtypes of gliomas while the predictive value of the IDH mutation in this context requires further study. In elderly patients with glioblastoma, the analysis of MGMT methylation status in two phase III trials suggests that this alteration may guide treatment decisions; however, this finding still needs confirmation in prospective studies. Omics and next-generation sequencing studies have identified additional potential predictive markers. In particular, IDH mutations, BRAF V600E mutations and FGFR gene fusions might predict efficacy of therapies targeted against these alterations.
Currently, the 1p/19q codeletion is the only well established predictive marker with clinical utility. However, it is likely that other molecular markers such as MGMT methylation, IDH mutation and those identified using omics and next-generation sequencing studies will further guide treatment decisions in adult gliomas.
本文综述了近年来关于成人胶质瘤分子标志物预测价值的研究进展，包括 1p/19q 缺失、MGMT 甲基化、IDH 突变以及基于组学和下一代测序研究发现的标志物。
在间变性少突胶质细胞瘤的放射治疗肿瘤学组和欧洲癌症研究与治疗组织临床试验的长期结果表明，1p/19q 缺失可预测早期 PCV（丙卡巴肼、洛莫司汀、长春新碱）化疗的总体生存获益。在这种情况下，还可以使用基于基因表达的胶质瘤分子亚型来预测这种获益，而 IDH 突变的预测价值在这种情况下需要进一步研究。在老年胶质母细胞瘤患者中，两项 III 期临床试验中 MGMT 甲基化状态的分析表明，这种改变可能指导治疗决策；然而，这一发现仍需要前瞻性研究的证实。组学和下一代测序研究已经确定了其他潜在的预测标志物。特别是 IDH 突变、BRAF V600E 突变和 FGFR 基因融合可能预测针对这些改变的治疗效果。
目前，1p/19q 缺失是唯一具有临床应用价值的确立的预测标志物。然而，MGMT 甲基化、IDH 突变以及基于组学和下一代测序研究发现的标志物等其他分子标志物可能会进一步指导成人胶质瘤的治疗决策。
