Identification of uterine leiomyoma-specific marker genes based on DNA methylation and their clinical application.

Shun Sato,Yoshiaki Yamagata,Hiroshi Tamura,Isao Tamura,Norihiro Sugino,Kosuke Jozaki,Hiromi Asada,Ryo Maekawa,Maki Okada,Lifa Lee

doi:10.1038/srep30652

Abstract

Differential diagnosis of uterine leiomyomas and leiomyosarcomas is needed to determine whether the uterus can be retained. Therefore, biomarkers for uterine leiomyomas, and reliable and objective diagnostic methods have been desired besides the pathological diagnosis. In the present study, we identified 12 genes specific to uterine leiomyomas based on DNA methylation. Using these marker genes specific to uterine leiomyomas, we established a hierarchical clustering system based on the DNA methylation level of the marker genes, which could completely differentiate between uterine leiomyomas and normal myometrium. Furthermore, our hierarchical clustering system completely discriminated uterine cancers and differentiated between uterine leiomyosarcomas and leiomyomas with more than 70% accuracy. In conclusion, this study identified DNA methylation-based marker genes specific to uterine leiomyomas, and our hierarchical clustering system using these marker genes was useful for differential diagnosis of uterine leiomyomas and leiomyosarcomas.

Highlights

Differential diagnosis of uterine leiomyomas and leiomyosarcomas is needed to determine whether the uterus can be retained
We further examined whether this hierarchical clustering system based on DNA methylation levels can be used to discriminate uterine cancers or uterine leiomyosarcomas from uterine leiomyomas
Among the 12 leiomyoma-specific marker genes, we attempted to select the most appropriate combination of the marker genes that best differentiate between leiomyomas and normal myometrium based on DNA methylation level of the marker gene

Summary

Introduction

Differential diagnosis of uterine leiomyomas and leiomyosarcomas is needed to determine whether the uterus can be retained. Women with uterine leiomyomas who wish to retain the uterus for future pregnancies are increasing in number. For such women, myomectomy is the recommended surgery. It has been reported that the uterine smooth muscle neoplasms diagnosed as benign leiomyomas metastasize in rare cases[10,11]. There is a need for differential diagnosis of uterine leiomyomas and leiomyosarcomas in addition to the pathological diagnosis, especially for women who wish to retain the uterus for future pregnancies

Methods

Results

Conclusion