Manchester Academic Health Science Centre, School of Cancer and Enabling Sciences, University of Manchester, The Christie NHS Foundation Trust, Withington, Manchester M20 4BX, UK.
Neuro Oncol. 2011 Apr;13(4):376-83. doi: 10.1093/neuonc/noq192. Epub 2011 Feb 2.
Current risk stratification schemas for medulloblastoma, based on combinations of clinical variables and histotype, fail to accurately identify particularly good- and poor-risk tumors. Attempts have been made to improve discriminatory power by combining clinical variables with cytogenetic data. We report here a pooled analysis of all previous reports of chromosomal copy number related to survival data in medulloblastoma. We collated data from previous reports that explicitly quoted survival data and chromosomal copy number in medulloblastoma. We analyzed the relative prognostic significance of currently used clinical risk stratifiers and the chromosomal aberrations previously reported to correlate with survival. In the pooled dataset metastatic disease, incomplete tumor resection and severe anaplasia were associated with poor outcome, while young age at presentation was not prognostically significant. Of the chromosomal variables studied, isolated 17p loss and gain of 1q correlated with poor survival. Gain of 17q without associated loss of 17p showed a trend to improved outcome. The most commonly reported alteration, isodicentric chromosome 17, was not prognostically significant. Sequential multivariate models identified isolated 17p loss, isolated 17q gain, and 1q gain as independent prognostic factors. In a historical dataset, we have identified isolated 17p loss as a marker of poor outcome and 17q gain as a novel putative marker of good prognosis. Biological markers of poor-risk and good-risk tumors will be critical in stratifying treatment in future trials. Our findings should be prospectively validated independently in future clinical studies.
目前基于临床变量和组织型组合的髓母细胞瘤风险分层方案未能准确识别特别良好和不良风险的肿瘤。已经尝试通过将临床变量与细胞遗传学数据相结合来提高区分能力。我们在此报告对所有先前报道的与髓母细胞瘤生存数据相关的染色体拷贝数的汇总分析。我们整理了以前明确引用髓母细胞瘤生存数据和染色体拷贝数的报告中的数据。我们分析了目前使用的临床风险分层因子和以前报道的与生存相关的染色体异常的相对预后意义。在汇总数据集，转移性疾病、不完全肿瘤切除和严重间变与不良预后相关，而发病时年龄较小则无预后意义。在研究的染色体变量中，孤立的 17p 缺失和 1q 的获得与不良生存相关。无 17p 丢失相关的 17q 获得显示出改善结局的趋势。最常报道的改变，是等臂染色体 17，与预后无关。顺序多变量模型确定孤立的 17p 缺失、孤立的 17q 获得和 1q 获得为独立的预后因素。在历史数据集，我们已经确定孤立的 17p 缺失是不良预后的标志物，而 17q 获得是良好预后的新的潜在标志物。不良风险和良好风险肿瘤的生物学标志物将是未来试验中分层治疗的关键。我们的发现应在未来的临床研究中独立进行前瞻性验证。
