<abstract xmlns="http://www.w3.org/1999/xhtml">

<sec id="j_raon-2017-0004_s_001">
<h3>Background</h3>
<p>Identifying the early genetic drivers can help diagnose glioma tumours in their early stages, before becoming malignant. However, there is emerging evidence that disturbance of epigenetic mechanisms also contributes to cell’s malignant transformation and cancer progression. Long non-coding RNAs are one of key epigenetic modulators of signalling pathways, since gene expression regulation is one of their canonical mechanisms. The aim of our study was to search new gliomagenesis-specific candidate lncRNAs involved in epigenetic regulation.</p>
</sec>
<sec id="j_raon-2017-0004_s_002">
<h3>Patients and methods</h3>
<p>We used a microarray approach to detect expression profiles of epigenetically involved lncRNAs on a set of 12 glioma samples, and selected <italic>LOC285758</italic> for further qPCR expression validation on 157 glioma samples of different subtypes. To establish if change in expression is a consequence of epigenetic alterations we determined methylation status of lncRNA’s promoter using MS-HRM. Additionally, we used the MLPA analysis for determining the status of known glioma biomarkers and used them for association analyses.</p>
</sec>
<sec id="j_raon-2017-0004_s_003">
<h3>Results</h3>
<p>In all glioma subtypes levels of LOC285758 were significantly higher in comparison to normal brain reference RNA, and expression was inversely associated with promoter methylation. Expression substantially differs between astrocytoma and oligodendroglioma, and is elevated in higher WHO grades, which also showed loss of methylation.</p>
</sec>
<sec id="j_raon-2017-0004_s_004">
<h3>Conclusions</h3>
<p>Our study revealed that lncRNA <italic>LOC285758</italic> changed expression in glioma is methylation-dependent and methylation correlates with WHO malignancy grade. Methylation is also distinctive between astrocytoma I-III and other glioma subtypes and may thus serve as an additional biomarker in glioma diagnosis.</p>
</sec>
</abstract>

Background
Identifying the early genetic drivers can help diagnose glioma tumours in their early stages, before becoming malignant. However, there is emerging evidence that disturbance of epigenetic mechanisms also contributes to cell’s malignant transformation and cancer progression. Long non-coding RNAs are one of key epigenetic modulators of signalling pathways, since gene expression regulation is one of their canonical mechanisms. The aim of our study was to search new gliomagenesis-specific candidate lncRNAs involved in epigenetic regulation.


Patients and methods
We used a microarray approach to detect expression profiles of epigenetically involved lncRNAs on a set of 12 glioma samples, and selected LOC285758 for further qPCR expression validation on 157 glioma samples of different subtypes. To establish if change in expression is a consequence of epigenetic alterations we determined methylation status of lncRNA’s promoter using MS-HRM. Additionally, we used the MLPA analysis for determining the status of known glioma biomarkers and used them for association analyses.


Results
In all glioma subtypes levels of LOC285758 were significantly higher in comparison to normal brain reference RNA, and expression was inversely associated with promoter methylation. Expression substantially differs between astrocytoma and oligodendroglioma, and is elevated in higher WHO grades, which also showed loss of methylation.


Conclusions
Our study revealed that lncRNA LOC285758 changed expression in glioma is methylation-dependent and methylation correlates with WHO malignancy grade. Methylation is also distinctive between astrocytoma I-III and other glioma subtypes and may thus serve as an additional biomarker in glioma diagnosis.

Expression of LOC285758, a potential long non-coding biomarker, is methylation-dependent and correlates with glioma malignancy grade

Radiology and Oncology

This work is licensed under the Creative Commons Attribution 4.0 International License.

Background
Identifying the early genetic drivers can help diagnose glioma tumours in their early stages, before becoming malignant. However, there is emerging...

Expression of LOC285758, a potential long non-coding biomarker, is methylation-dependent and correlates with glioma malignancy grade

Article Category: Research Article

Publicado en línea: 14 ene 2017

Páginas: 331 - 341

Recibido: 24 oct 2016

Aceptado: 22 nov 2016

DOI: https://doi.org/10.1515/raon-2017-0004

© 2017 Alenka Matjasic, Mara Popovic, Bostjan Matos and Damjan Glavac

This work is licensed under the Creative Commons Attribution 4.0 International License.