Somatic mutations in IFN-γ-Signal molecules in human uterine leiomyosarcoma
Name
somatic-mutations-in-IFN-γ-Signal-molecules-in-human-uterine-leiomyosarcoma.pdf
Description
Published version
Size
715.08 KB
Format
Adobe PDF
Checksum (MD5)
d65bd8bb242b39eaace71afb6f1240b0
Author(s)
Tonegawa, Susumu
Date Issued
September 28, 2018
Journal
Annals of biotechnology
Publisher
MedDocs Publishers LLC
Citation
Hayashi, Takuma et al. “Somatic mutations in IFN-γ-Signal molecules in human uterine leiomyosarcoma.” Annals of biotechnology 1 (2018): 1014 © 2018 The Author(s)
Version
Final published version
Abstract
Uterus Leiomyosarcoma (uLMS), unfortunately, is a dis-ease with a poor prognosis. In the report of the Ministry of Health, Labor and Welfare, the 50% survival time (mOS) summarized from Stage I to Stage IV was 31months. Pre-operative diagnosis of uLMS is very difficult. Although it is diagnosed as “uterine fibroids”, it is not uncommon in cases where the uterine leiomyosarcoma is definitely diagnosed again after surgical hysterectomy or removal of myoma. Hu-man uLMS is neoplastic malignancy that typically arises in tissues of mesenchymal origin. The identification of novel molecular mechanism leading to human uLMS formation and the establishment of new clinical therapies has been hampered by several critical points. Mice with a homozy-gous deficiency for Proteasome beta subunit (Psmb)9/β1i spontaneously develop uLMS-like neoplasm. The use of re-search findings with mouse model has been successful in increasing our knowledge and understanding of how alterations, in relevant oncogenic, tumor suppressive, and signal pathways directly impact sarcomagenesis. The experiments with human clinical materials revealed a defective expres-sion of PSMB9/? 1i in human uLMS that was traced to the IFN-γ pathway and the specific effect of somatic mutations of Janus kinase (JAK) 1molecule and/or promoter region on the locus cording PSMB9/β1i gene. Understanding the bio-logical characters of human uLMS may lead to identification of new diagnostic candidates or therapeutic targets against human uLMS.
MIT Department
Picower Institute for Learning and Memory
Terms of Use
Creative Commons Attribution 4.0 International license
Persistent DSpace Link
DOI of Published Version
https://doi.org/10.33582/2637-4927/1014
