CLONING of TUMOR SUPPRESSOR GENE LOCUS for ENDOMETRIAL CARCINOMA on CHROMOSOME 1

鉴定CHR基因候选抑制基因S的基因座。1、利用微细胞融合技术，将带有间质Q臂缺失(del-1Q)或来源于Chr.1q的亚染色体可转移片段(30A3 STF)的新标记的人1号染色体导入人子宫内膜癌细胞系HHUA。Del-1Q和30A2 STF具有诱导细胞生长停滞和类似衰老细胞的形态改变的潜力。这些结果表明，对HHUA细胞具有衰老诱导活性的目的基因定位于D1S510-D1S237或D1S103-D1S547所定义的CHR 1Q区域。为了进一步确定候选基因座，我们对61例手术切除的子宫内膜癌样本进行了缺失重排筛选。最后，我们在D1S225和D1S459所定义的1q41-42区域发现了高发的杂合性缺失。YAC克隆也能诱导细胞衰老。利用该YAC DNA，或位于YAC内的ABAC DNA，从正常人子宫内膜cDNA文库中分离出几个克隆。其中，我们在许多子宫内膜癌中发现了一个初级序列发生改变的候选基因。

To identify the locus of a candidate suppressor gene (s) on chr. 1, A neo-tagged human chromosome 1 that carried an interstitial q arm deletion (del-1q) or a subchromosomal transferrable fragment (30A3 STF) derived from a chr.1q was transferred into human endometrial cancer cell line, HHUA via microcell fusion. The del- 1q and the 30A2 STF had the potential to induce the growth arrest and the morphologixal changes analogous to senescent cells. These results indicate that the target gene that has senescence-inducing activity for HHUA cells is localized to the chr 1q region defined by D1S510-D1S237 or D1S103-D1S547. To further define the candidate locus, we screened 61 surgically removed endometrial cancer samples for rearrangements of deletions. Finally, we found a high incidence of LOH in the 1q41-42 region defined by the STS D1S225 and D1S459.After identifying a YAC clone, designated 748H11by Research Genetics, which keeps the both D1S225 and D1S459 markers, we transferred it into HHUA. The YAC clone could also induce the cellular senescence. By using this YAC DNA, or aBAC DNA which region is located within the YAC, several cDNA clones were isolated from the normal human endometrial cDNA library. Among them, we found one candidate which primary sequence was altered in many endometrial cancers.