Genomics

Dataset Information

148

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 characteristic 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 that 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 two components. Hallmarks of DNA methylation abnormality of 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 these diseases. Overall design: We used laser capture microdissection (LCM) to separate the two components of uterine carcinosarcoma (UCS) samples from 3 patients. We used two complementary next-generation sequencing-based methods, methylated DNA immunoprecipitation sequencing (MeDIP-seq) and methylation-sensitive restriction enzyme digestion sequencing (MRE-seq), to construct genome-wide DNA methylation maps at single-CpG resolution in these components. We also generared methylome of endometrial stromal sarcoma (ESS).

INSTRUMENT(S): Illumina Genome Analyzer IIx (Homo sapiens)

SUBMITTER: Ting Wang 

PROVIDER: GSE86505 | GEO | 2017-03-08

SECONDARY ACCESSION(S): PRJNA342097

REPOSITORIES: GEO

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Publications

Whole-Genome DNA Methylation Profiling Identifies Epigenetic Signatures of Uterine Carcinosarcoma.

Li Jing J   Xing Xiaoyun X   Li Daofeng D   Zhang Bo B   Mutch David G DG   Hagemann Ian S IS   Wang Ting T  

Neoplasia (New York, N.Y.) 20170112 2


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,  ...[more]

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