Yin Xiao-lu, Pang Jesse Chung-sean, Ng Ho-keung
Department of Anatomical and Cellular Pathology, Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong, China.
Oncogene. 2002 Feb 21;21(9):1461-8. doi: 10.1038/sj.onc.1205204.
To identify critical tumor suppressor loci that are associated with the development of medulloblastoma, we performed a comprehensive genome-wide allelotype analysis in a series of 12 medulloblastomas. Non-random allelic imbalances were identified on chromosomes 7q (58.3%), 8p (66.7%), 16q (58.3%), 17p (58.3%) and 17q (66.7%). Comparative genomic hybridization analysis confirmed that allelic imbalances on 8p, 16q and 17p were due to loss of genetic materials. Finer deletion mapping in an expanded series of 23 medulloblastomas localized the common deletion region on 8p to an interval of 18.14 cM on 8p22-23.2. We then searched within the region of loss on 8p for loci that might contain homozygous deletion using comparative duplex PCR. An overlapping homozygous deletion region was identified in a 1.8 cM interval on 8p22-23.1, between markers D8S520 and D8S1130, in two medulloblastomas. This region of homozygous deletion also encompasses the 1.4 cM minimal deletion region detected on 8p in ductal carcinoma in situ of breast. In conclusion, we reported for the first time a detailed deletion mapping on 8p in medulloblastoma and have identified a region of homozygous deletion on 8p22-23.1 that is likely to contain a critical tumor suppressor gene involved in the development of medulloblastoma.
为了鉴定与髓母细胞瘤发生相关的关键肿瘤抑制基因座，我们对12例髓母细胞瘤进行了全面的全基因组等位基因分型分析。在7号染色体长臂（58.3%）、8号染色体短臂（66.7%）、16号染色体长臂（58.3%）、17号染色体短臂（58.3%）和17号染色体长臂（66.7%）上发现了非随机的等位基因失衡。比较基因组杂交分析证实，8号染色体短臂、16号染色体长臂和17号染色体短臂上的等位基因失衡是由于遗传物质缺失所致。在扩大至23例髓母细胞瘤的系列研究中进行更精细的缺失定位，将8号染色体短臂上的常见缺失区域定位到8p22 - 23.2上18.14 cM的区间。然后，我们使用比较双链PCR在8号染色体短臂的缺失区域内搜索可能包含纯合缺失的基因座。在两个髓母细胞瘤中，于8号染色体短臂22 - 23.1上标记D8S520和D8S1130之间的1.8 cM区间内鉴定出一个重叠的纯合缺失区域。该纯合缺失区域还包含在乳腺导管原位癌8号染色体短臂上检测到的1.4 cM最小缺失区域。总之，我们首次报道了髓母细胞瘤8号染色体短臂上的详细缺失定位，并鉴定出8p22 - 23.1上的一个纯合缺失区域，该区域可能包含一个参与髓母细胞瘤发生的关键肿瘤抑制基因。
