Non-Coding RNAs as Prognostic Markers for Endometrial Cancer

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Abstract

Endometrial cancer (EC) has been classified over the years, for prognostic and therapeutic purposes. In recent years, classification systems have been emerging not only based on EC clinical and pathological characteristics but also on its genetic and epigenetic features. Noncoding RNAs (ncRNAs) are emerging as promising markers in several cancer types, including EC, for which their prognostic value is currently under investigation and will likely integrate the present prognostic tools based on protein coding genes. This review aims to underline the importance of the genetic and epigenetic events in the EC tumorigenesis, by expounding upon the prognostic role of ncRNAs.

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Integrated Genomic Characterization of Endometrial Carcinoma

Nikolaus Schultz (2014)

Summary We performed an integrated genomic, transcriptomic, and proteomic characterization of 373 endometrial carcinomas using array- and sequencing-based technologies. Uterine serous tumors and ~25% of high-grade endometrioid tumors have extensive copy number alterations, few DNA methylation changes, low ER/PR levels, and frequent TP53 mutations. Most endometrioid tumors have few copy number alterations or TP53 mutations but frequent mutations in PTEN, CTNNB1, PIK3CA, ARID1A, KRAS and novel mutations in the SWI/SNF gene ARID5B. A subset of endometrioid tumors we identified had a dramatically increased transversion mutation frequency, and newly identified hotspot mutations in POLE. Our results classified endometrial cancers into four categories: POLE ultramutated, microsatellite instability hypermutated, copy number low, and copy number high. Uterine serous carcinomas share genomic features with ovarian serous and basal-like breast carcinomas. We demonstrated that the genomic features of endometrial carcinomas permit a reclassification that may impact post-surgical adjuvant treatment for women with aggressive tumors.

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Functions of DNA methylation: islands, start sites, gene bodies and beyond.

Peter A. Jones (2012)

DNA methylation is frequently described as a 'silencing' epigenetic mark, and indeed this function of 5-methylcytosine was originally proposed in the 1970s. Now, thanks to improved genome-scale mapping of methylation, we can evaluate DNA methylation in different genomic contexts: transcriptional start sites with or without CpG islands, in gene bodies, at regulatory elements and at repeat sequences. The emerging picture is that the function of DNA methylation seems to vary with context, and the relationship between DNA methylation and transcription is more nuanced than we realized at first. Improving our understanding of the functions of DNA methylation is necessary for interpreting changes in this mark that are observed in diseases such as cancer.

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Chromatin modifications and their function.

Tony Kouzarides (2007)

The surface of nucleosomes is studded with a multiplicity of modifications. At least eight different classes have been characterized to date and many different sites have been identified for each class. Operationally, modifications function either by disrupting chromatin contacts or by affecting the recruitment of nonhistone proteins to chromatin. Their presence on histones can dictate the higher-order chromatin structure in which DNA is packaged and can orchestrate the ordered recruitment of enzyme complexes to manipulate DNA. In this way, histone modifications have the potential to influence many fundamental biological processes, some of which may be epigenetically inherited.

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Author and article information

Contributors

Konrad Huppi: Role: Academic Editor

Journal

Journal ID (nlm-ta): Int J Mol Sci

Journal ID (iso-abbrev): Int J Mol Sci

Journal ID (publisher-id): ijms

Title: International Journal of Molecular Sciences

Publisher: MDPI

ISSN (Electronic): 1422-0067

Publication date (Electronic): 19 March 2021

Publication date Collection: March 2021

Volume: 22

Issue: 6

Electronic Location Identifier: 3151

Affiliations

[1 ]Institute of Molecular Biology and Pathology, Italian National Research Council (CNR-IBPM), 00185 Rome, Italy; roberto.piergentili@ 123456cnr.it

[2 ]Department of Anatomical, Histological, Forensic and Orthopedic Sciences, “Sapienza” University of Rome, Viale Regina Elena 336, 00161 Rome, Italy

[3 ]Gynecology and Obstetric Department, Azienda USL Toscana Centro, Santo Stefano Hospital, 59100 Prato, Italy; annafranca.cavaliere@ 123456uslcentro.toscana.it

[4 ]Obstetrics and Gynecology Department, USL Roma2, Sant’Eugenio Hospital, 00144 Rome, Italy; fabrizio.signore@ 123456aslroma2.it

[5 ]Fondazione Policlinico Universitario A. Gemelli IRCCS, Gynecologic Oncology Unit, 00168 Rome, Italy; giovanni.scambia@ 123456policlinicogemelli.it

[6 ]Universita’ Cattolica Del Sacro Cuore, 00168 Rome, Italy

[7 ]Gynecology and Obstetric Department, Azienda USL Toscana Centro, Santa Maria Annunziata Hospital, 50012 Florence, Italy; alberto.mattei@ 123456uslcentro.toscana.it (A.M.); federica.perelli@ 123456uslcentro.toscana.it (F.P.)

[8 ]Unit of Forensic Toxicology (UoFT), Department of Anatomical, Histological, Forensic and Orthopedic Sciences, Sapienza University, 00161 Rome, Italy; enrico.marinelli@ 123456uniroma1.it

[9 ]Department of Urology, Misericordia Hospital, 58100 Grosseto, Italy; 85cate@ 123456live.it

Author notes

[* ]Correspondence: simona.zaami@ 123456uniroma1.it ; Tel.: +39-327-3385-804

[†]

These authors contributed equally to this work.

Author information

Roberto Piergentili https://orcid.org/0000-0001-7584-2171

Simona Zaami https://orcid.org/0000-0001-5741-7139

Article

Publisher ID: ijms-22-03151

DOI: 10.3390/ijms22063151

PMC ID: 8003471

PubMed ID: 33808791

SO-VID: f6676d14-16d9-45b6-a29a-a466f3acca5c

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Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

Non-Coding RNAs as Prognostic Markers for Endometrial Cancer

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Abstract

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Most cited references 238

Integrated Genomic Characterization of Endometrial Carcinoma

Functions of DNA methylation: islands, start sites, gene bodies and beyond.

Chromatin modifications and their function.

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