Detection of mitochondrial DNA mutations in the tumor and cerebrospinal fluid of medulloblastoma patients.
Detection of mitochondrial DNA mutations in the tumor and cerebrospinal fluid of medulloblastoma patients.
复制标题
DOI：
--
复制
发表时间：
2003-07
期刊：
影响因子：
11.2
通讯作者：
L. Wong;M. Lueth;Xiao-Nan Li;C. Lau;H. Vogel
中科院分区：
文献类型：
--
作者：
L. Wong;M. Lueth;Xiao-Nan Li;C. Lau;H. Vogel
髓母细胞瘤是儿童最常见的恶性脑肿瘤。虽然预后有了很大的改善，但肿瘤的脑膜外扩散仍然是生存的一个显著的负面预测因素。线粒体DNA （mtDNA）突变已在许多类型的人类肿瘤中检测到，但未在髓母细胞瘤中检测到。我们利用时间温度梯度凝胶电泳分析了15例髓母细胞瘤的全线粒体基因组，并对其中8例的脑脊液样本进行了分析。15例中有6例（40%）在每个肿瘤中至少有一个mtDNA突变。共检测到18个体细胞mtDNA突变，其中一个肿瘤有11个突变，其中9个是新的。分析的8份脑脊液样本中有7份显示mtDNA突变。一名患者在治疗结束时收集的脑脊液中显示持续的mtDNA突变，当时没有疾病的证据，5个月后复发。相比之下，治疗结束时脑脊液样本显示没有可检测到的mtDNA突变或与肿瘤不同的突变的患者继续无病。我们的研究结果表明mtDNA突变在成神经管细胞瘤中经常发现。脑脊液中检测到的mtDNA改变可作为监测疾病进展和预测复发的敏感标志物。
Medulloblastoma is the most common malignant brain tumor in children. Although the prognosis has improved considerably, leptomeningeal spread of the tumor remains a significantly negative predictor of survival. Mitochondrial DNA (mtDNA) mutations have been detected in many types of human tumors but not in medulloblastomas. Using temporal temperature gradient gel electrophoresis, we have analyzed the entire mitochondrial genome in 15 cases of medulloblastoma and the corresponding cerebrospinal fluid (CSF) samples in 8 of 15 cases. Six of 15 cases (40%) showed at least one mtDNA mutation in each of the tumors. A total of 18 somatic mtDNA mutations was detected with one of the tumors having 11 mutations, of which 9 were novel. Seven of 8 CSF samples that were analyzed showed mtDNA mutations. One patient who showed persistent mtDNA mutation in the CSF collected at the end of therapy when there was no evidence of disease had a relapse 5 months later. In contrast, patients whose end-of-therapy CSF samples that showed either no detectable mtDNA mutation or different mutations from that of the tumor continue to be disease free. Our results demonstrate that mtDNA mutations are frequently found in medulloblastomas. The mtDNA alterations detected in CSF may be used as sensitive markers to monitor disease progression and predict relapse.