635DETECTION OF SOMATIC MUTATIONS IN INTERFERON-γ SIGNAL MOLECULES IN HUMAN UTERINE LEIOMYOSARCOMAHuman uterine leiomyosarcoma (Ut-LMS) is neoplastic malignancy that typically arises in tissues of mesenchymal origin. The identification of novel molecular mechanism leading to human Ut-LMS formation and the establishment of new therapies has been hampered by several critical points. We earlier reported that mice with a homozygous deficiency for proteasome subunit beta type (PSMB) 9, an interferon (IFN)- inducible factor, spontaneously develop Ut-LMS. The use of research findings of the experiment with mouse model has been successful in increasing our knowledge and understanding of how alterations, in relevant oncogenic, tumor suppressive, and signaling pathways directly impact sarcomagenesis. The IFN- signaling pathway is important for control of tumor growth and invasion and has been implicated in several malignant tumors. In this study, experiments with human tissues revealed a defective PSMB9 expression in human Ut-LMS that was traced to the IFN- signaling pathway and the specific effect of somatic mutations of Janus kinase (JAK) 1 molecule or PSMB9 gene promoter region on the PSMB9 gene transcriptional activation. Understanding the molecular mechanisms of human Ut-LMS may lead to identification of new diagnostic candidates or therapeutic targets in human Ut-LMSyoyoyo224@hotmail.comResearch672015PSMB9,Somatic mutation,Uterine leoimyosarcoma,Leiomyoma,MyometriumTakuma Hayashi,Akiko Horiuchi,Kenji Sano,Nobuyoshi Hiraoka,Tomoyuki Ichimura,Nobuo Yaegashi,Hiroyuki Aburatani,Ikuo KonishiDept. of Immunology and Infectious Disease, Shinshu University Graduate School of Medicine, Japan Science and Technology Agency (JST), Tokyo, 102-0076 Japan.,Horiuchi Ladies Clinic, Japan Science and Technology Agency (JST), Tokyo, 102-0076 Japan.,Dept. of Laboratory Medicine, Shinshu University Hospital, Japan Science and Technology Agency (JST), Tokyo, 102-0076 Japan.,Pathology Division, National Cancer Center Research Institute, Japan Science and Technology Agency (JST), Tokyo, 102-0076 Japan., Dept. of Obstetrics and Gynecology, Osaka City University Graduate School of Medicine, Japan Science and Technology Agency (JST), Tokyo, 102-0076 Japan.,Dept. of Obstetrics and Gynecology, Tohoku University Graduate School of Medicine, Dept. of Obstetrics and Gynecology, Tohoku University Graduate School of Medicine,Dept. of Obstetrics and Gynecology, Shinshu University, School of Medicine, Dept. of Obstetrics and Gynecology, Tohoku University Graduate School of Medicine,8Dept. of Obstetrics and Gynecology, Kyoto Un