Infrequent genomic rearrangement and normal expression of the putative RB1 gene in retinoblastoma tumors-猫眼课题宝

视网膜母细胞瘤中假定的 RB1 基因不常见的基因组重排和正常表达

DOI：

发表时间：

1988

期刊：

Molecular and Cellular Biology

影响因子：

5.3

通讯作者：

中科院分区：

生物学2区

文献类型：

作者：

A. Goddard;H. Bałakier;M. Canton;J. Dunn;J. Squire;E. Reyes;A. Becker;R. A. Phillips;B. Gallie

视网膜母细胞瘤(RB)是当一个基因(RB1)的两个等位基因都发生突变并无法正常功能时发生的肿瘤。最近，Friend等人。[S.H.Friend，R.Bernards，S.Rogelj，R.A.Weinberg，J.M.Rapaport，D.M.Albert，and T.P.Dryja，Nature(London)32：643-646,1986]报道了一个4.7R基因的克隆，该基因具有预期的RB1基因的一些特性，即在肿瘤中高频率(30%)的基因组重排，并且在所有被研究的RB肿瘤中没有信息。为了扩展该基因的特征，我们使用4.7R探针寻找DNA的基因组重排，并研究4.7R基因在RB肿瘤、RB患者发生的骨肉瘤(OS)以及其他正常和恶性组织中的表达。在34例以前未报道的RB和OS肿瘤中，我们只观察到4例(12%)存在基因组异常。在17例RB瘤中有12例表达4.7R转录本，2例OS瘤中有2例表达4.7R转录本，所有非RB瘤和正常组织均检测到4.7R转录本。我们无法证实Lee等人报道的4.7R截短消息在RB肿瘤中的高频率。(Lee W.H.Lee，R.Bookstein，F.Hong，L.J.Young，J.Y.Shaw和E.Y.Lee，Science 235：1394-1399,1987)和冯等人。(Y.K.Fung，A.L.Murphree，A.Tang，J.Qian，S.H.Hinrichs和W.F.Benedict，Science 236：1657-1661,1987)，但确实证实了在RB细胞系Y79中存在截短的转录本。在Southern杂交显示正常的Rb和Rb相关的OS肿瘤中，26例中有2例(12%)有异常转录，这使得Southern和Northern(RNA)印迹分析可检测到的4.7R基因异常的联合频率为22%。

Retinoblastoma (RB) tumors develop when both alleles of a gene (RB1) are mutated and unable to function normally. Recently, Friend et al. [S. H. Friend, R. Bernards, S. Rogelj, R. A. Weinberg, J. M. Rapaport, D. M. Albert, and T. P. Dryja, Nature (London) 32:643-646, 1986] reported the cloning of a gene, 4.7R, with some properties expected for the RB1 gene, namely, a high frequency (30%) of genomic rearrangements in tumors and absence of message in all RB tumors examined. To extend the characterization of this gene, we used 4.7R probes to search for genomic rearrangements of DNA and to study the expression of the 4.7R gene in RB tumors, osteosarcoma (OS) tumors arising in RB patients, and other normal and malignant tissues. In 34 previously unreported RB and OS tumors arising in RB patients, we observed only four (12%) with genomic abnormalities. Transcripts of 4.7R were present in 12 of 17 RB tumors, 2 of 2 OS tumors, and all non-RB tumors and normal tissues tested. We were unable to confirm the high frequency of truncated messages of 4.7R in RB tumors reported by Lee et al. (W. H. Lee, R. Bookstein, F. Hong, L. J. Young, J. Y. Shaw, and E. Y. Lee, Science 235:1394-1399, 1987) and Fung et al. (Y. K. Fung, A. L. Murphree, A. Tang, J. Qian, S. H. Hinrichs, and W. F. Benedict, Science 236:1657-1661, 1987) but did confirm the presence of a truncated transcript in the RB cell line Y79. Of the RB and RB-related OS tumors which appeared normal on Southern blots, 2 of 26 or 12% had abnormal transcripts, giving a combined frequency of 22% abnormalities in the 4.7R gene detectable by Southern and Northern (RNA) blot analyses.