title: Whole-Genome DNA Methylation Profiling Identifies Epigenetic Signatures of Uterine Carcinosarcoma.
abstract: Uterine carcinosarcoma (UCS) is a form of endometrial cancer simultaneously exhibiting carcinomatous and sarcomatous elements, but the underlying molecular and epigenetic basis of this disease is poorly understood. We generated complete DNA methylomes for both the carcinomatous and the sarcomatous components of three UCS samples separated by laser capture microdissection and compared DNA methylomes of UCS with those of normal endometrium as well as methylomes derived from endometrioid carcinoma, serous endometrial carcinoma, and endometrial stromal sarcoma. We identified epigenetic lesions specific to carcinosarcoma and specific to its two components. Hallmarks of DNA methylation abnormalities in UCS included global hypomethylation, especially in repetitive elements, and hypermethylation of tumor suppressor gene promoters. Among these, aberrant DNA methylation of MIR200 genes is a key feature of UCS. The carcinoma component of UCS was characterized by hypermethylation of promoters of EMILIN1, NEFM, and CLEC14A, genes that are associated with tumor vascularization. In contrast, DNA methylation changes of PKP3, FAM83F, and TCP11 were more characteristic of the sarcoma components. Our findings highlight the epigenetic signatures that distinguish the two components of UCS, providing a valuable resource for investigation of this disease.
authors.affiliation: Department of Genetics, Washington University School of Medicine, St. Louis, MO; Center for Genome Sciences and Systems Biology, Washington University School of Medicine, St. Louis, MO; Center for Translational Medicine, Second Military Medical University, Shanghai, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Li
authors.affiliation: Department of Genetics, Washington University School of Medicine, St. Louis, MO; Center for Genome Sciences and Systems Biology, Washington University School of Medicine, St. Louis, MO.
authors.forename: Xiaoyun
authors.initials: X
authors.lastname: Xing
authors.affiliation: Department of Genetics, Washington University School of Medicine, St. Louis, MO; Center for Genome Sciences and Systems Biology, Washington University School of Medicine, St. Louis, MO.
authors.forename: Daofeng
authors.initials: D
authors.lastname: Li
authors.affiliation: Department of Genetics, Washington University School of Medicine, St. Louis, MO; Center for Genome Sciences and Systems Biology, Washington University School of Medicine, St. Louis, MO.
authors.forename: Bo
authors.initials: B
authors.lastname: Zhang
authors.affiliation: Department of Obstetrics & Gynecology, Washington University School of Medicine, St. Louis, MO.
authors.forename: David G
authors.initials: DG
authors.lastname: Mutch
authors.affiliation: Department of Obstetrics & Gynecology, Washington University School of Medicine, St. Louis, MO; Department of Pathology & Immunology, Washington University School of Medicine, St. Louis, MO. Electronic address: ihagemann@path.wustl.edu.
authors.forename: Ian S
authors.initials: IS
authors.lastname: Hagemann
authors.affiliation: Department of Genetics, Washington University School of Medicine, St. Louis, MO; Center for Genome Sciences and Systems Biology, Washington University School of Medicine, St. Louis, MO.
authors.forename: Ting
authors.initials: T
authors.lastname: Wang
mesh_terms: D002296:Carcinosarcoma / Q000235:genetics* / Q000473:pathology; D016000:Cluster Analysis; D019295:Computational Biology / Q000379:methods; D018899:CpG Islands; D019175:DNA Methylation; D000066630:Ectopic Gene Expression; D016889:Endometrial Neoplasms / Q000235:genetics / Q000473:pathology; D044127:Epigenesis, Genetic; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D055106:Genome-Wide Association Study; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D035683:MicroRNAs / Q000235:genetics; D060787:Neoplasm Grading; D011401:Promoter Regions, Genetic; D015203:Reproducibility of Results; D059467:Transcriptome; D014594:Uterine Neoplasms / Q000235:genetics* / Q000473:pathology
chemical_list: C533896:MIRN200 microRNA, human; D035683:MicroRNAs