Dynamic inosinome profiles reveal novel patient stratification and gender-specific differences in glioblastoma View Full Text


Ontology type: schema:ScholarlyArticle     


Article Info

DATE

2019-12

AUTHORS

Domenico Alessandro Silvestris, Ernesto Picardi, Valeriana Cesarini, Bruno Fosso, Nicolò Mangraviti, Luca Massimi, Maurizio Martini, Graziano Pesole, Franco Locatelli, Angela Gallo

ABSTRACT

BACKGROUND: Adenosine-to-inosine (A-to-I) RNA editing is an essential post-transcriptional mechanism mediated by ADAR enzymes that have been recently associated with cancer. RESULTS: Here, we characterize the inosinome signature in normal brain and de novo glioblastoma (GBM) using new metrics that re-stratify GBM patients according to their editing profiles and indicate this post-transcriptional event as a possible molecular mechanism for sexual dimorphism in GBM. We find that over 85% of de novo GBMs carry a deletion involving the genomic locus of ADAR3, which is specifically expressed in the brain. By analyzing RNA editing and patient outcomes, an intriguing gender-dependent link appears, with high editing of Alus shown to be beneficial only in male patients. We propose an inosinome-based molecular stratification of GBM patients that identifies two different GBM subgroups, INO-1 and INO-2, which can identify novel high-risk gender-specific patient groups for which more aggressive treatments may be necessary. CONCLUSIONS: Our data provide a detailed picture of RNA editing landscape in normal brain and GBM, exploring A-to-I RNA editing regulation, disclosing unexpected editing implications for GBM patient stratification and identification of gender-dependent high-risk patients, and suggesting COG3 I/V as an eligible site for future personalized targeted gene therapy. More... »

PAGES

33

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  • Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1186/s13059-019-1647-x

    DOI

    http://dx.doi.org/10.1186/s13059-019-1647-x

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1112097245

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/30760294


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