title: Genomic landscape of endometrial stromal sarcoma of uterus.
abstract: Although recurrent gene fusions such as JAZF1-JJAZ1 are considered driver events for endometrial stromal sarcoma (ESS) development, other genomic alterations remain largely unknown. In this study, we performed whole-exome sequencing, transcriptome sequencing and copy number profiling for five ESSs (three low-grade ESS (LG-ESS) and two undifferentiated uterine sarcomas (UUSs)). All three LG-ESSs exhibited either one of JAZF1-SUZ12, JAZF1-PHF1 and MEAF6-PHF1 fusions, whereas the two UUSs did not. All ESSs except one LG-ESS exhibited copy number alterations (CNAs), many of which encompassed cancer-related genes. In UUSs, five CNAs encompassing cancer-related genes (EZR, CDH1, RB1, TP53 and PRKAR1A) accompanied their expressional changes, suggesting that they might stimulate UUS development. We found 81 non-silent mutations (35 from LG-ESSs and 46 from UUSs) that included 15 putative cancer genes catalogued in cancer-related databases, including PPARG and IRF4 mutations. However, they were non-recurrent and did not include any well-known mutations, indicating that point mutations may not be a major driver for ESS development. Our data show that gene fusions and CNAs are the principal drivers for LG-ESS and USS, respectively, but both may require additional genomic alterations including point mutations. These differences may explain the different biologic behaviors between LG-ESS and UUS. Our findings suggest that ESS development requires point mutations and CNAs as well as the gene fusions.
authors.affiliation: Department of Pathology, College of Medicine, The Catholic University of Korea, Seoul 137-701, Republic of Korea.
authors.forename: Youn Jin
authors.initials: YJ
authors.lastname: Choi
authors.affiliation: Department of Cancer Evolution Research Center, College of Medicine, The Catholic University of Korea, Seoul 137-701, Republic of Korea.|Department of Integrated Research Center for Genome Polymorphism, College of Medicine, The Catholic University of Korea, Seoul 137-701, Republic of Korea.
authors.forename: Seung-Hyun
authors.initials: SH
authors.lastname: Jung
authors.affiliation: Department of Pathology, College of Medicine, The Catholic University of Korea, Seoul 137-701, Republic of Korea.
authors.forename: Min Sung
authors.initials: MS
authors.lastname: Kim
authors.affiliation: Department of Cancer Evolution Research Center, College of Medicine, The Catholic University of Korea, Seoul 137-701, Republic of Korea.|Department of Integrated Research Center for Genome Polymorphism, College of Medicine, The Catholic University of Korea, Seoul 137-701, Republic of Korea.
authors.forename: In-Pyo
authors.initials: IP
authors.lastname: Baek
authors.affiliation: Department of Medical Informatics, College of Medicine, The Catholic University of Korea, Seoul 137-701, Republic of Korea.
authors.forename: Jae-Keun
authors.initials: JK
authors.lastname: Rhee
authors.affiliation: Department of Hospital Pathology, College of Medicine, The Catholic University of Korea, Seoul 137-701, Republic of Korea.
authors.forename: Sung Hak
authors.initials: SH
authors.lastname: Lee
authors.affiliation: Department of Obstetrics/Gynecology, College of Medicine, The Catholic University of Korea, Seoul 137-701, Republic of Korea.
authors.forename: Soo Young
authors.initials: SY
authors.lastname: Hur
authors.affiliation: Department of Medical Informatics, College of Medicine, The Catholic University of Korea, Seoul 137-701, Republic of Korea.
authors.forename: Tae-Min
authors.initials: TM
authors.lastname: Kim
authors.affiliation: Department of Cancer Evolution Research Center, College of Medicine, The Catholic University of Korea, Seoul 137-701, Republic of Korea.|Department of Integrated Research Center for Genome Polymorphism, College of Medicine, The Catholic University of Korea, Seoul 137-701, Republic of Korea.|Department of Microbiology, College of Medicine, The Catholic University of Korea, Seoul 137-701, Republic of Korea.
authors.forename: Yeun-Jun
authors.initials: YJ
authors.lastname: Chung
authors.affiliation: Department of Pathology, College of Medicine, The Catholic University of Korea, Seoul 137-701, Republic of Korea.|Department of Cancer Evolution Research Center, College of Medicine, The Catholic University of Korea, Seoul 137-701, Republic of Korea.
authors.forename: Sug Hyung
authors.initials: SH
authors.lastname: Lee
mesh_terms: D000328:Adult; D000368:Aged; D015331:Cohort Studies; D056915:DNA Copy Number Variations; D016889:Endometrial Neoplasms / Q000235:genetics*; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D008875:Middle Aged; D015514:Oncogene Proteins, Fusion / Q000235:genetics; D018203:Sarcoma, Endometrial Stromal / Q000235:genetics*
chemical_list: D015514:Oncogene Proteins, Fusion
keywords: copy number; endometrial stromal sarcoma; genome; mutation; whole exome