Mutational analysis of the TrkA gene in prostate cancer
Mutational analysis of the TrkA gene in prostate cancer
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DOI：
10.1002/(sici)1097-0045(19980801)36:3
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发表时间：
1998-08-01
期刊：
影响因子：
2.8
通讯作者：
Isaacs, JT
中科院分区：
文献类型：
--
作者：
George, DJ;Suzuki, H;Isaacs, JT
背景TrkA是神经生长因子（NGF）的高亲和力酪氨酸激酶受体，已被认为是几种肿瘤中的癌基因。在前列腺癌中，NGF/TrkA信号通路的抑制剂导致肿瘤生长抑制。相反，在正常前列腺中抑制trk通路则没有效果。正常和恶性前列腺之间这种差异的一种解释是TrkA在前列腺癌中发生突变，改变了其功能。为了测试这种可能性，筛选人原发性前列腺癌中TrkA基因突变的证据，以确定该基因如何在前列腺癌中被激活。应用单链构象多态性技术对42例原发性前列腺癌患者的基因组DNA进行了筛选。在鉴定出异常带型的样品中，使用肿瘤DNA和从相同患者的正常组织分离的DNA重复筛选。通过对异常迁移条带的直接测序证实了遗传变化。虽然体细胞突变没有确定在任何的外显子筛选，四个多态性检测在三个不同的外显子。这些多态性中的一些发生在大多数筛选的患者中，但与对照组分离的DNA相比，它们的频率相似。TrkA的基因突变似乎在前列腺癌中该途径的激活中不起重要作用。然而，在其他遗传不稳定的前列腺肿瘤DNA中没有突变表明，完整的NGF/TrkA通路可能在前列腺癌的发展中很重要。前列腺36：172 - 180，1998年。(C)1998 Wiley-Liss，Inc.
BACKGROUND. TrkA, the high affinity, tyrosine kinase receptor for nerve growth factor, (NGF) has been implicated as an oncogene in several neoplasms. In prostate cancer, inhibitors of the NGF/TrkA signal pathway results in tumor growth inhibition. In contrast, inhibition of this trk pathway in the normal prostate produces no effect. One explanation for this difference between normal and malignant prostate is that TrkA is mutated in prostate cancer, changing its function. To test this possibility human primary prostate cancers were screened for evidence of mutations in the TrkA gene to identify how this gene might be activated in prostate cancer.METHODS. Single-strand conformation polymorphism was used to screen genomic DNA, isolated from 42 human primary prostate cancers. In samples in which an aberrant banding pattern was identified, the screen was repeated using both the tumor DNA and DNA isolated from normal tissue of the same patients. Genetic changes were confirmed by direct sequencing of the aberrantly migrating bands.RESULTS. Although somatic mutations were not identified in any of the exons screened, four polymorphisms were detected in three different exons. Some of these polymorphisms occurred in the majority of the patients screened, but their frequencies were similar when compared with DNA isolated from a control group.CONCLUSIONS. Genetic mutations of TrkA do not seem to play a significant role in activation of this pathway in prostate cancer. However, the absence of mutations in otherwise genetically unstable prostate tumor DNA suggests that intact NGF/TrkA pathways may be important in prostate cancer development. Prostate 36:172-180, 1998. (C) 1998 Wiley-Liss, Inc.