Prediction of central nervous system embryonal tumour outcome based on gene expression
Prediction of central nervous system embryonal tumour outcome based on gene expression
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DOI：
10.1038/415436a
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发表时间：
2002-01-24
期刊：
影响因子：
64.8
通讯作者：
Golub, TR
中科院分区：
文献类型：
--
作者：
Pomeroy, SL;Tamayo, P;Golub, TR
中枢神经系统（CNS）的胚胎性肿瘤是一组异质性肿瘤，其生物学特性知之甚少，仅根据形态学表现进行诊断也存在争议。例如，髓母细胞瘤是儿童期最常见的恶性脑肿瘤，但其发病机制尚不清楚，其与其他胚胎性CNS肿瘤的关系存在争议（1，2），患者对治疗的反应难以预测（3）。我们通过开发一个基于来自99个患者样本的DNA微阵列基因表达数据的分类系统来解决这些问题。在这里，我们表明，髓母细胞瘤是不同的分子从其他脑肿瘤，包括原始神经外胚层肿瘤（PNDT），非典型畸胎瘤/横纹肌样肿瘤（AT/RTs）和恶性胶质瘤。以前未被认识的证据支持通过激活Sonic Hedgehog（SHH）通路从小脑颗粒细胞衍生成髓细胞瘤也被揭示。我们进一步表明，儿童髓母细胞瘤的临床结果是高度可预测的基础上，他们的肿瘤在诊断的基因表达谱。
Embryonal tumours of the central nervous system (CNS) represent a heterogeneous group of tumours about which little is known biologically, and whose diagnosis, on the basis of morphologic appearance alone, is controversial. Medulloblastomas, for example, are the most common malignant brain tumour of childhood, but their pathogenesis is unknown, their relationship to other embryonal CNS tumours is debated(1,2), and patients' response to therapy is difficult to predict(3). We approached these problems by developing a classification system based on DNA microarray gene expression data derived from 99 patient samples. Here we demonstrate that medulloblastomas are molecularly distinct from other brain tumours including primitive neuroectodermal tumours (PNETs), atypical teratoid/rhabdoid tumours (AT/RTs) and malignant gliomas. Previously unrecognized evidence supporting the derivation of medulloblastomas from cerebellar granule cells through activation of the Sonic Hedgehog (SHH) pathway was also revealed. We show further that the clinical outcome of children with medulloblastomas is highly predictable on the basis of the gene expression profiles of their tumours at diagnosis.