CANCER CELL:进一步细化成神经管细胞瘤亚型,促进个性化治疗

2017-06-13 MedSci MedSci原创

成神经管细胞瘤(MB)是儿童中最常见的恶性脑肿瘤。 历史上,基于临床特征和肿瘤组织病理学,MB患者已被分层为平均风险(AR)或高风险(HR),HR-MB患者接受较高剂量的放射治疗(RT)。对于AR-MB和HR-MB,常规治疗即最大程度的安全肿瘤切除术,RT至全脑和脊柱,化疗的5年总生存率(OS)分别为80%和70%。

成神经管细胞瘤(MB)是儿童中最常见的恶性脑肿瘤。 历史上,基于临床特征和肿瘤组织病理学,MB患者已被分层为平均风险(AR)或高风险(HR),HR-MB患者接受较高剂量的放射治疗(RT)。对于AR-MB和HR-MB,常规治疗即最大程度的安全肿瘤切除术,RT至全脑和脊柱,化疗的5年总生存率(OS)分别为80%和70%。因此,必须克服两个基本面临的挑战,以改善对MB患儿的照顾。 首先是确定可以有效治疗并且可以省略或减少RT剂量的MB患者。第二个挑战是提高对目前治疗效果不佳的MB患者的生存率。在本期“癌细胞”中,Cavalli等通过大型MB数据集的综合分析分析,对四个已知的MB子组中的每一个,进一步界定了肿瘤间的异质性。这进一步的对MB亚组内的肿瘤的异质性的认识,是通过个性化风险适应治疗,改善MB患者结局的关键一步。展望未来,在临床试验的背景下,建立基于这些发现的生物标志物来确定MB亚型是至关重要的,有助于对均匀治疗的患者群体的结果进行前瞻性研究。

虽然分子亚组已经改变成神经管细胞瘤分类,亚组内的异质性程度是未知的。适用于全基因组DNA甲基化的相似性网络融合(SNF)和跨越763个初级样本的基因表达数据识别出非常均匀的患者群,支持成神经管细胞瘤亚型的存在。在整合体细胞拷贝数变化和每个群集特异性的临床特征之后,我们鉴定了12种不同的成神经管细胞瘤亚型。使用SNF的综合分析进一步描绘了第4组成神经管细胞瘤组3,通过分析个体数据类型并不明显。确定了具有不同结果和生物学的Sonic Hedgehog成神经管细胞瘤的婴儿的两种明确亚型。 通过综合聚类确定的成神经管细胞瘤亚型对未来临床试验的分层具有重要意义。

原文出处:

Abhishek Bavle,and D. Williams Parsons,et al.Intertumoral Heterogeneity within Medulloblastoma Subgroups.[J].cancer cell 2017 June 13;357 DOI:http://dx.doi.org/10.1016/j.ccell.2017.05.013


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    2017-08-28 维他命
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