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

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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.