TY - JOUR
T1 - Whole-Genome DNA Methylation Profiling Identifies Epigenetic Signatures of Uterine Carcinosarcoma
AU - Li, Jing
AU - Xing, Xiaoyun
AU - Li, Daofeng
AU - Zhang, Bo
AU - Mutch, David G.
AU - Hagemann, Ian S.
AU - Wang, Ting
N1 - Publisher Copyright:
© 2016 The Authors
PY - 2017
Y1 - 2017
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85016000910&partnerID=8YFLogxK
U2 - 10.1016/j.neo.2016.12.009
DO - 10.1016/j.neo.2016.12.009
M3 - Article
C2 - 28088687
AN - SCOPUS:85016000910
SN - 1522-8002
VL - 19
SP - 100
EP - 111
JO - Neoplasia (United States)
JF - Neoplasia (United States)
IS - 2
ER -