Mutirangura A, Pornthanakasem W, Sriuranpong V, Supiyaphun P, Voravud N
Department of Anatomy, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand.
Int J Cancer. 1998 Oct 5;78(2):153-6. doi: 10.1002/(sici)1097-0215(19981005)78:2<153::aid-ijc5>3.0.co;2-y.
The main objective of this study was to determine the precise frequency of chromosome 14q loss of heterozygosity in nasopharyngeal carcinomas and to define its minimal deletion regions. Thirty-nine tumors were selected for PCR-based deletion mapping using 19 microsatellite polymorphic markers spanning the long arm of this chromosome. Loss of heterozygosity for at least one marker was observed in 29 (74.4%) tumors, while 24 of these tumors displayed partial loss and provided an informative basis for detailed deletion mapping. Three minimal regions of loss were delineated, the first defined by markers D14S278 and D14S288, the second being between D14S51 and the telomere. These data confirmed 2 potential tumor-suppressor-gene loci at 14q12-13 and 14q32. Interestingly, the third region of loss was located at the T-cell-receptor delta-chain locus. This may reflect another tumor-suppressor-gene locus at 14q11.2, or may be the consequence of a specific genomic rearrangement of this region. In addition, these allelic losses occurred with high frequency in all tumor grades and stages and in all histological sub-types. These findings suggest that the genetic alteration of chromosome 14 is common and crucial during nasopharyngeal-carcinoma development.
本研究的主要目的是确定鼻咽癌中14号染色体杂合性缺失的确切频率,并确定其最小缺失区域。使用跨越该染色体长臂的19个微卫星多态性标记,选择了39个肿瘤进行基于聚合酶链反应(PCR)的缺失定位。在29个(74.4%)肿瘤中观察到至少一个标记的杂合性缺失,其中24个肿瘤显示部分缺失,为详细的缺失定位提供了信息基础。划定了三个缺失最小区域,第一个由标记D14S278和D14S288界定,第二个位于D14S51和端粒之间。这些数据证实了14q12 - 13和14q32处的两个潜在肿瘤抑制基因位点。有趣的是,第三个缺失区域位于T细胞受体δ链基因座。这可能反映了14q11.2处的另一个肿瘤抑制基因位点,或者可能是该区域特定基因组重排的结果。此外,这些等位基因缺失在所有肿瘤分级和分期以及所有组织学亚型中均高频发生。这些发现表明,14号染色体的基因改变在鼻咽癌发生过程中很常见且至关重要。