Myopodin, a synaptopodin homologue, is frequently deleted in invasive prostate cancers
Myopodin, a synaptopodin homologue, is frequently deleted in invasive prostate cancers
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DOI：
10.1016/s0002-9440(10)63006-4
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发表时间：
2001-11-01
影响因子：
6
通讯作者：
Luo, JH
中科院分区：
文献类型：
--
作者：
Lin, F;Yu, YP;Luo, JH
前列腺癌是美国男性癌症相关死亡的主要原因之一。像其他恶性肿瘤一样，前列腺癌在其发展过程中也有多种异常的基因改变。虽然杂合性缺失或等位基因缺失在前列腺癌中经常被发现，但迄今为止很少有基因被确定为浸润性前列腺癌发展的关键基因。在这篇报告中，我们使用了最近开发的技术，“差异减法链”，对侵袭性前列腺癌中缺失的序列进行全基因组搜索。在被删除的序列中，我们发现一个序列在我们检测的前列腺癌中有50%被删除。我们利用该探针特异性引物筛选Genebridge 4仓鼠辐射面板，将该序列定位到染色体4q25上，随后鉴定出包含编码myopodin序列的54kb最小共同缺失区。序列分析表明myopodin与synaptopodin具有显著的同源性，synaptopodin是一种与足细胞和神经元分化密切相关的蛋白质。进一步的研究表明，myopodin基因在侵袭性前列腺癌病例中经常发生完全或部分缺失（31例中有25例，或80%）。统计分析表明myopodin的缺失与前列腺癌的侵袭性高度相关，因此可能有望成为前列腺癌的重要预后标志物。
Prostate cancer Is one of the leading causes of cancer-related deaths for men in the United States. Like other malignancies, prostate cancer is underscored by a variety of aberrant genetic alterations during its development. Although loss of heterozygosity or allelic loss is frequently Identified among prostate cancers, few genes have been identified thus far as critical to the development of invasive prostate cancers. in this report, we used the recently developed technology, the "differential subtraction chain," to perform a genome-wide search for sequences that are deleted in an aggressive prostate cancer. Among the deleted sequences, we found that one sequence was deleted in > 50% of prostate cancers we tested. We mapped this sequence to chromosome 4q25 by screening the Genebridge 4 hamster radiation panel with primers specific to this probe, and subsequently identify a 54-kb minimal common deletion region that contains the sequence encoding myopodin. Sequence analysis indicates that myopodin shares significant homology with synaptopodin, a protein closely associated with podocyte and neuron differentiation. Further study shows that frequent complete or partial deletions of the myopodin gene occurred among invasive prostate cancer cases (25 of 31 cases, or 80%). Statistical analysis indicates that deletion of myopodin is highly correlated with the invasiveness of prostate cancers, and thus may hold promise as an important prognostic marker for prostate cancers.