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一个假定的肿瘤抑制基因在8号染色体短臂亚端粒区域的定位。

Localization of a putative tumor suppressor gene in the sub-telomeric region of chromosome 8p.

作者信息

Sunwoo J B, Sun P C, Gupta V K, Schmidt A P, El-Mofty S, Scholnick S B

机构信息

Department of Otolaryngology - Head and Neck Surgery, Washington University School of Medicine, St Louis, Missouri, USA.

出版信息

Oncogene. 1999 Apr 22;18(16):2651-5. doi: 10.1038/sj.onc.1202838.

Abstract

Several regions of chromosome arm 8p are frequently deleted in a variety of human malignancies including those of the prostate, head and neck, lung, and colon, suggesting that there is more than one tumor suppressor gene on this chromosome arm. Both laryngeal and oral squamous cell carcinomas exhibit three distinct and nonoverlapping regions of deletion on 8p. We have further refined the localization of the putative suppressor in 8p23 by using eight microsatellite loci to create a high resolution deletion map of 150 squamous cell carcinomas of the larynx and oral cavity. These new data demonstrate that there are two distinct classes of deletion within this relatively small region of the chromosome and suggest two possible locations for the gene within the D8S264 to D8S1788 interval. We also determined that there is little difference between the allelic loss frequencies of microsatellites mapping near the telomeric ends of other chromosome arms and loci mapping to more centromere proximal regions of the same arm. These data suggest that the high allelic loss frequencies seen at 8p23 loci are not the result of a generalized instability of chromosome ends and are instead consistent with the activation of a specific suppressor gene.

摘要

在包括前列腺癌、头颈癌、肺癌和结肠癌在内的多种人类恶性肿瘤中,8号染色体短臂的几个区域经常发生缺失,这表明该染色体臂上存在不止一个肿瘤抑制基因。喉癌和口腔鳞状细胞癌在8p上均表现出三个不同且不重叠的缺失区域。我们通过使用八个微卫星位点,进一步精确确定了位于8p23的假定抑制基因的定位,从而构建了150例喉和口腔鳞状细胞癌的高分辨率缺失图谱。这些新数据表明,在该染色体相对较小的区域内存在两种不同类型的缺失,并提示该基因在D8S264至D8S1788区间内的两个可能位置。我们还确定,位于其他染色体臂端粒末端附近的微卫星与位于同一臂更靠近着丝粒近端区域的位点之间,等位基因缺失频率几乎没有差异。这些数据表明,在8p23位点观察到的高等位基因缺失频率并非染色体末端普遍不稳定的结果,而是与特定抑制基因的激活一致。

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