Many gene changes found in cancer.
Many gene changes found in cancer.
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在癌症中发现了许多基因变化。
DOI：
10.1126/science.2595361
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发表时间：
1989
期刊：
影响因子：
56.9
通讯作者：
J. Marx
中科院分区：
文献类型：
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作者：
J. Marx
一组研究人员克隆了一个可能导致Wilms‘s肿瘤的基因，该肿瘤占所有儿童肾癌的85%。在11号染色体上发现的候选基因具有肿瘤抑制特性；它只是第三个被发现的此类抑制基因。然而，最近的克隆并没有完全解决Wilms的肿瘤如何开始的问题，因为有证据表明，其他几个基因的变化(一些甚至不在11号染色体上)可能与肿瘤的开始有关。最近在美国人类遗传学学会年会上报道了可能的抑制基因的分离和鉴定。这项工作是由麻省理工学院大卫·霍斯曼实验室的凯瑟琳·考尔和她的同事以及科罗拉多大学的卡罗尔·琼斯领导的一个团队进行的。威尔姆斯的肿瘤通常在2到5岁之间被诊断出来，患上这种肿瘤的平均风险约为8000人中有1人。虽然预后总体良好，但在一小部分患者中，死亡率超过50%。Housman研究小组通过比较正常肾细胞和肾母细胞瘤细胞系中的染色体和表达谱来进行鉴定。在一些肿瘤细胞系中，新发现的基因在11号染色体短臂上的11p13区域的两个副本中都缺失；在这些细胞中检测到很少或根本没有来自该基因的信使RNA。在正常细胞中，该基因以两个拷贝存在并得到表达。这些发现表明，在正常细胞中，这对基因抑制了潜在的肿瘤形成；当它们缺失时，肿瘤可能开始形成。由于两个拷贝都必须改变，基因才能在肿瘤形成中发挥作用，因此Wilms的基因是隐性的。唯一已知的另一个隐性肿瘤抑制基因是视网膜母细胞瘤基因，于1986年被克隆。(第二个已知的肿瘤抑制基因P53似乎至少在某些情况下表现为显性(见相关报道))。然而，视网膜母细胞瘤基因和Wilms的肿瘤基因之间的差异可能比它们的相似之处更引人注目。只有一个基因与视网膜母细胞瘤的形成有关，而细胞遗传学和分子证据表明，Wilms基因只是与该肿瘤相关的几个基因之一。休斯敦MD Anderson癌症中心的Grady Saunders和Louise Strong在11p13区域发现了另一个可能与Wilms‘s肿瘤有关的序列；其他研究小组在11号染色体的其他区域发现了可能也起作用的异常。也有证据表明，其他染色体上的基因可能与此有关。去年，两个研究小组发现，在一些家庭中
A team of investigators has cloned a gene that may be the cause ofWilms' tumor, which accounts for 85% ofall kidney cancers in children. The candidate gene, found on chromosome 11, has tumor-suppressing properties; it is only the third such suppressor gene to be identified. The recent cloning, however, does not fully resolve the question ofhow Wilms' tumor begins, because there is evidence that changes in several other genes (some not even on chromosome 11) may be involved in tumor initiation. The isolation and characterization of the putative suppressor gene were reported at the recent annual meeting ofthe American Society ofHuman Genetics. The work was carried out by a team led by Katherine Call and her colleagues in David Housman's lab at the Massachusetts Institute of Technology, along with Carol Jones at the University of Colorado.Wilms' tumor is most often diagnosed between the ages of 2 and 5, and the average risk for developing the tumor is about 1 in 8000. Although the prognosis is generally good, among a small subset of patients the death rate exceeds 50%. The Housman group based their identification on a comparison of chromosomes and expression profiles in normal kidney cells and cell lines derived from Wilms' tumor cells. In some tumor-cell lines, the newly identified gene was missing from both copies of the 11p13 region on the short arm of chromosome 11; little or no messenger RNA from the gene was detected in those cells. In normal cells the gene was present in two copies and was expressed. These findings suggest that in normal cells the pair ofgenes suppresses potential tumor formation; when they are missing, a tumor may begin to form. Since both copies must be altered for the gene to playa role in tumor formation, the Wilms' gene is recessive. The only other known recessive tumor-suppressing gene is the retinoblastoma gene, cloned in 1986.(The second known tumor suppressor gene, p53, seems to behave, at least in some cases, in a dominant fashion [see accompanying story]). The differences between the retinoblastoma gene and the Wilms' tumor gene, however, may be more striking than their similarities. Only one gene has been implicated in the formation of retinoblastoma, whereas cytogenetic and molecular evidence suggests that the Wilms' gene is only one of several genes associated with that tumor. Grady Saunders and Louise Strong of the MD Anderson Cancer Center in Houston have found another sequence in the 11p13 region that may be implicated in Wilms' tumor; other groups have found abnormalities in other regions of chromosome 11 that may also play a role. There is also evidence that genes on other chromosomes may be involved. Last year, two groups found that in some families