Oncotarget

Research Papers:

Epigenetic signatures differentiate uterine and soft tissue leiomyosarcoma

Nesrin M. Hasan, Anup Sharma, Nensi M. Ruzgar, Hari Deshpande, Kelly Olino, Sajid Khan and Nita Ahuja _

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Oncotarget. 2021; 12:1566-1579. https://doi.org/10.18632/oncotarget.28032

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Abstract

Nesrin M. Hasan1, Anup Sharma1, Nensi M. Ruzgar2, Hari Deshpande3, Kelly Olino1, Sajid Khan1,4 and Nita Ahuja1

1 Department of Surgery, Yale University School of Medicine, New Haven, CT, USA

2 Yale University School of Medicine, New Haven, CT, USA

3 Department of Internal Medicine, Section of Medical Oncology, Yale University School of Medicine, New Haven, CT, USA

4 Department of Surgery, Section of Hepatopancreatobiliary and Mixed Tumors, Yale University School of Medicine, New Haven, CT, USA

Correspondence to:

Nita Ahuja,email: nita.ahuja@yale.edu

Keywords: leiomyosarcoma; epigenetics; DNA methylation; gene expression; uterine leiomyosarcoma

Received: May 07, 2021     Accepted: July 13, 2021     Published: August 03, 2021

Copyright: © 2021 Hasan et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

ABSTRACT

Leiomyosarcomas (LMS) are diverse, rare, and aggressive mesenchymal soft tissue sarcomas. Epigenetic alterations influence multiple aspects of cancer, however epigenetic profiling of LMS has been limited. The goal of this study was to delineate the molecular landscape of LMS for subtype-specific differences (uterine LMS (ULMS) vs soft tissue LMS (STLMS)) based on integrated analysis of DNA methylation and gene expression to identify potential targets for therapeutic intervention and diagnosis. We identified differentially methylated and differentially expressed genes associated with ULMS and STLMS using DNA methylation and RNA-seq data from primary tumors. Two main clusters were identified through unsupervised hierarchical clustering: ULMS-enriched cluster and STLMS-enriched cluster. The integrated analysis demonstrated 34 genes associated with hypermethylation of the promoter CpG islands and downregulation of gene expression in ULMS or STLMS. In summary, these results indicate that differential DNA methylation and gene expression patterns are associated with ULMS and STLMS. Further studies are needed to delineate the contribution of epigenetic regulation to LMS subtype-specific gene expression and determine the roles of the differentially methylated and differentially expressed genes as potential therapeutic targets or biomarkers.


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