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Genet is classification of gliomas based on whole genome analysis and neurogenes is-related gene expressions

Genet 是基于全基因组分析的神经胶质瘤分类，神经基因是相关基因表达

基本信息

批准号：
16390419
负责人：
UEKI Keisuke
金额：
$ 9.15万
依托单位：
Dokkyo Medical University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
2004
资助国家：
日本
起止时间：
2004 至 2006
项目状态：
已结题

项目摘要

Over 60 gliomas were resected and analyzed. The diagnosis was performed in combination with genetic analysis on chromosomes 1p/19q/10q, which were known to correlate with oligodendroglial histological features and expression status of neuron-related genes in our previous studies. While treating the patients in the same protocol (PAV/RT 60Gy for GBM and PAV only for oligodendroglial tumors), clinical response was closely monitored. We attempted primary cultures for more than 10 gliomas. However, the established cultured cells showed different genetic alterations from the original tumors. Cells from 1p/19q-losing gliomas (n=3) did not show 1p/19q loss, which did not allow us to study gene-expression changes after chemotherapy in vitro, as was proposed in the project design. Meanwhile, the similar phenomenon, loss of "1p/19qloss" at the recurrence of oligodendroglioma, was detected in 2 cases. The underlying mechanisms for this interesting phenomenon should be examined in the future.Whole … More -genome examination for allele-specific copy number changes using Gene Imbalance Mapping method (GIM) developed by Aburatani et al. was performed on 22 glioma samples. In oligodendrogliomas, GIM clearly showed that pure low grade oligodendrogliomas are the tumors harbor whole arm losses of 1p and 19q as their only genetic alterations. With histological changes to more anaplastic morphology, oligodendrogliomas show other genetic alterations such as 14q loss, 4p/4q loss, 9p loss, gradually becoming anaplastic oligodendrogliomas. Progression from grade 2 to 3 is therefore rather continuous, and GIM is an excellent method for the diagnosis of oligodendrogliomas. In glioblastomas, numerous loci showing homozygous deletion was detected, where currently unidentified tumor suppressor genes may be located. One such loci, 12q, was picked up and a few number of candidate genes are now being evaluated.Unfortunately, the clinical data including survival are not yet obtained at this point, and comparison of genetic analysis and clinical response, the center theme of this project, should await summarization of clinical data. Less

共切除胶质瘤60余例，并进行分析。诊断结合染色体1 p/19 q/10 q的遗传分析进行，这些染色体在我们以前的研究中已知与少突胶质细胞的组织学特征和神经元相关基因的表达状态相关。在以相同的方案（PAV/RT 60 Gy用于GBM和PAV仅用于少突胶质细胞肿瘤）治疗患者的同时，密切监测临床反应。我们尝试了10多个胶质瘤的原代培养。然而，建立的培养细胞显示出与原始肿瘤不同的遗传改变。来自1 p/19 q丢失胶质瘤的细胞（n=3）没有显示1 p/19 q丢失，这不允许我们研究体外化疗后的基因表达变化，正如项目设计中所提出的那样。2例少突胶质细胞瘤复发时也出现类似的“1 p/19 qloss”缺失现象。今后应研究这一有趣现象的基本机制。 ...更多信息使用Aburatani等人开发的基因不平衡作图方法（GIM）对22个胶质瘤样品进行等位基因特异性拷贝数变化的基因组检查。在少突胶质细胞瘤中，GIM清楚地表明，纯低级别少突胶质细胞瘤是肿瘤具有1 p和19 q的全臂缺失作为其唯一的遗传改变。随着组织学改变为更多间变性形态，少突胶质细胞瘤显示其他遗传改变，如14 q丢失，4p/4 q丢失，9 p丢失，逐渐成为间变性少突胶质细胞瘤。因此，从2级到3级的进展是相当连续的，GIM是诊断少突胶质细胞瘤的一种很好的方法。在胶质母细胞瘤中，检测到许多显示纯合缺失的位点，其中可能存在目前未鉴定的肿瘤抑制基因。12 q基因座已被挑选出来，目前正在对一些候选基因进行评估。遗憾的是，目前还没有获得包括生存率在内的临床数据，本项目的中心主题--遗传分析与临床反应的比较，还有待于临床数据的总结。少