Phillips Heidi S, Kharbanda Samir, Chen Ruihuan, Forrest William F, Soriano Robert H, Wu Thomas D, Misra Anjan, Nigro Janice M, Colman Howard, Soroceanu Liliana, Williams P Mickey, Modrusan Zora, Feuerstein Burt G, Aldape Ken
Department of Tumor Biology and Angiogenesis, Genentech, Inc., South San Francisco, California 94080, USA.
Cancer Cell. 2006 Mar;9(3):157-73. doi: 10.1016/j.ccr.2006.02.019.
Previously undescribed prognostic subclasses of high-grade astrocytoma are identified and discovered to resemble stages in neurogenesis. One tumor class displaying neuronal lineage markers shows longer survival, while two tumor classes enriched for neural stem cell markers display equally short survival. Poor prognosis subclasses exhibit markers either of proliferation or of angiogenesis and mesenchyme. Upon recurrence, tumors frequently shift toward the mesenchymal subclass. Chromosomal locations of genes distinguishing tumor subclass parallel DNA copy number differences between subclasses. Functional relevance of tumor subtype molecular signatures is suggested by the ability of cell line signatures to predict neurosphere growth. A robust two-gene prognostic model utilizing PTEN and DLL3 expression suggests that Akt and Notch signaling are hallmarks of poor prognosis versus better prognosis gliomas, respectively.
先前未描述的高级别星形细胞瘤预后亚类被识别出来，并发现其类似于神经发生的阶段。一个显示神经元谱系标志物的肿瘤类别生存期更长，而两个富含神经干细胞标志物的肿瘤类别生存期同样较短。预后不良的亚类表现出增殖、血管生成或间充质的标志物。复发时，肿瘤常转向间充质亚类。区分肿瘤亚类的基因的染色体位置与亚类之间的DNA拷贝数差异平行。细胞系特征预测神经球生长的能力提示了肿瘤亚型分子特征的功能相关性。一个利用PTEN和DLL3表达的强大的双基因预后模型表明，Akt和Notch信号分别是预后不良与预后较好的胶质瘤的标志。
