Tsang Y S, Lo K W, Leung S F, Choi P H, Fong Y, Lee J C, Huang D P
Department of Anatomical Pathology, The Chinese University of Hong Kong, Hong Kong SAR, China.
Int J Cancer. 1999 Oct 29;83(3):305-8. doi: 10.1002/(sici)1097-0215(19991029)83:3<305::aid-ijc3>3.0.co;2-d.
Nasopharyngeal carcinoma (NPC) is rare in most parts of the world, but prevalent in Southern China. Although this disease poses a serious health problem in our population, the genetic alterations that lead to the development of NPC have yet to be defined. In a comparative genomic hybridization (CGH) study on NPC by our group, loss of the long arm of chromosome 13 has been identified as a frequent event. To investigate further the involvement of this genetic alteration in NPC tumorigenesis, we examined 31 primary NPC tumours by LOH analysis with a panel of 13 microsatellite polymorphic markers distributed along the long arm of chromosome 13. It was found that 19/31 tumours (60%) showed LOH for markers on chromosome 13q. The highest frequency of LOH was found at loci D13S133 (53.6%) on 13q14.3 and D13S796 (38.5%) on 13q32-34. Two distinct smallest deletion regions were delineated: the first region between D13S133 and D13S119 at 13q14.3-22, and the second region between D13S317 and D13S285 at 13q31-34. Our findings show that LOH of 13q is a common event in NPC and that at least 2 putative tumour-suppressor loci may be present on 13q. Mapping of the critical regions of these loci suggests that some candidate tumour-suppressor genes on 13q, other than Rb and BRCA2, may be involved in the development of NPC.
鼻咽癌(NPC)在世界大部分地区都很罕见,但在中国南方却很普遍。尽管这种疾病在我国人群中构成了严重的健康问题,但导致鼻咽癌发生的基因改变尚未明确。在我们小组对鼻咽癌进行的比较基因组杂交(CGH)研究中,已确定13号染色体长臂缺失是一个常见事件。为了进一步研究这种基因改变在鼻咽癌发生中的作用,我们用一组分布在13号染色体长臂上的13个微卫星多态性标记,通过杂合性缺失(LOH)分析检测了31例原发性鼻咽癌肿瘤。结果发现,19/31例肿瘤(60%)在13q染色体上的标记显示出杂合性缺失。杂合性缺失频率最高的位点是13q14.3上的D13S133(53.6%)和13q32 - 34上的D13S796(38.5%)。确定了两个不同的最小缺失区域:第一个区域在13q14.3 - 22的D13S133和D13S119之间,第二个区域在13q31 - 34的D13S317和D13S285之间。我们的研究结果表明,13q的杂合性缺失在鼻咽癌中是一个常见事件,并且13q上可能存在至少2个假定的肿瘤抑制基因座。这些基因座关键区域的定位表明,13q上除了Rb和BRCA2之外的一些候选肿瘤抑制基因可能参与了鼻咽癌 的发生。