Dong Z, Pang Jc-S, Ng M H, Poon W S, Zhou L, Ng H-K
1Department of Anatomical and Cellular Pathology, Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong, China.
Br J Cancer. 2004 Sep 13;91(6):1105-11. doi: 10.1038/sj.bjc.6602093.
Loss of the short arm of chromosome 1 is a hallmark of oligodendroglial tumours (OTs). Deletion mapping studies in OTs have revealed multiple commonly deleted regions on chromosome 1p, suggesting that there are more than one tumour suppressor gene. To map critical deletion regions on 1p, a series of 25 OTs were examined for loss of heterozygosity (LOH) on 19 polymorphic markers across the 1p arm using microsatellite analysis. Our study revealed that 60% of tumours had LOH of all informative markers on 1p and identified one tumour showing LOH at telomeric markers only. Since this deletion region lies in one of the critical deletion intervals defined previously, we then screened another series of 27 OTs specifically at 1p36.3 for LOH using nine polymorphic markers. A total of 12% (six out of 52) of tumours were found to carry interstitial deletions. The allelic status and the deletion breakpoints in these tumours with interstitial deletion were further verified by fluorescent in situ hybridisation. The small overlapping intervals facilitated the delineation of two contiguous minimally deleted regions of 0.76 Mb, defined by D1S468 and D1S2845, and of 0.41 Mb, bound by D1S2893 and D1S1608, on 1p36.31-36.32. Based on current reference human genome sequence these deletion regions have been sequenced almost to entirety and contain eight annotated genes. TP73, DFFB and SHREW1 are the only known genes located in these deletion regions, while the others are uncharacterised novel genes. In conclusion, our study has narrowed down the critical tumour suppressor loci on 1p36.3, in which two minimally deleted regions are mapped, and markedly reduced the number of candidate genes to be screened for their involvement in OT development.
1号染色体短臂缺失是少突胶质细胞瘤（OTs）的一个标志。对OTs的缺失图谱研究揭示了1号染色体短臂（1p）上多个常见的缺失区域，这表明存在不止一个肿瘤抑制基因。为了绘制1p上的关键缺失区域，使用微卫星分析对一系列25个OTs进行检测，以确定1p臂上19个多态性标记的杂合性缺失（LOH）情况。我们的研究表明，60%的肿瘤在1p上所有信息性标记均存在LOH，并且鉴定出1例仅在端粒标记处出现LOH的肿瘤。由于该缺失区域位于先前定义的关键缺失区间之一，我们随后使用9个多态性标记专门针对1p36.3对另一系列27个OTs进行LOH筛查。共发现12%（52个中有6个）的肿瘤存在间质缺失。通过荧光原位杂交进一步验证了这些存在间质缺失肿瘤的等位基因状态和缺失断点。这些小的重叠区间有助于勾勒出1p36.31 - 36.32上两个相邻的最小缺失区域，一个由D1S468和D1S2845界定，大小为0.76 Mb，另一个由D1S2893和D1S1608界定，大小为0.41 Mb。基于当前的人类参考基因组序列，这些缺失区域几乎已全部测序，包含8个注释基因。TP73、DFFB和SHREW1是这些缺失区域中仅有的已知基因，其他则是未表征的新基因。总之，我们的研究缩小了1p36.3上关键肿瘤抑制基因座的范围，确定了两个最小缺失区域，并显著减少了为筛选参与OT发生发展的候选基因数量。
