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

被引:31
作者
Li, Jing [1 ,2 ,3 ]
Xing, Xiaoyun [1 ,2 ]
Li, Daofeng [1 ,2 ]
Zhang, Bo [1 ,2 ]
Mutch, David G. [4 ,5 ]
Hagemann, Ian S. [1 ]
Wang, Ting [1 ,2 ,3 ]
机构
[1] Washington Univ, Sch Med, Dept Genet, St Louis, MO 63130 USA
[2] Washington Univ, Sch Med, Ctr Genome Sci & Syst Biol, St Louis, MO 63130 USA
[3] Second Mil Med Univ, Ctr Translat Med, Shanghai, Peoples R China
[4] Washington Univ, Sch Med, Dept Obstet & Gynecol, St Louis, MO USA
[5] Washington Univ, Sch Med, Dept Pathol & Immunol, St Louis, MO USA
来源
NEOPLASIA | 2017年 / 19卷 / 02期
基金
美国国家卫生研究院;
关键词
CANCER-CELLS; HYPOMETHYLATION; EXPRESSION; CARCINOMA; HYPERMETHYLATION; ACTIVATION; DETERMINES; PROMOTERS; MUTATIONS; PHENOTYPE;
D O I
10.1016/j.neo.2016.12.009
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
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.
引用
收藏
页码:100 / 111
页数:12
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